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Abstract The aim of our study was to evaluate if the response to follicular GnRH agonist (GnRHa) trigger be used to predict intracycle ovarian response in GnRH antagonist cycles among women undergoing fertility preservation IVF. We conducted a prospective study of 146 GnRH antagonist oocyte pickup (OPU) cycles to evaluate GnRHa stimulation test (GAST). On day 2 of the cycle, basal E2 were measured, followed by injection of 0.2 mg GnRHa as part of the initial ovarian stimulation. 12 h later blood sampling was repeated (GAST E3). E2 response was used as test parameter. The major outcome was the number of mature cryopreserved oocytes. We found a linear correlation between both GAST E3 level and GAST E3/E2 ratio and number of M2 oocytes. ROC curve analysis of GAST E3, GAST E3/E2 ratio, AFC and day 3 FSH for > 15 M2 and 15 M2 oocytes, AUC value of 0.8. Patients with GAST E3 ≤ 384 pmol/l has 58.6% risk to obtain 708 pmol/l have 66% chance for freezing > 15 oocytes. The response to single GnRHa administration during GnRH antagonist cycle can be used as biomarker of ovarian reserve. This simple, widely available marker, which reflect the estradiol response of small follicles, might predict the response of the specific cycle, and can potentially be used to adjust the treatment dose. Trial registration number: 0304-20-ASF.

Free-Space Optical (FSO) communications have emerged as a viable solution to complement conventional communication technologies, mainly due to their high transmission rates, ease of implementation, low cost, and unlicensed spectrum. However, FSO technology faces significant challenges in achieving the initial alignment between the transceivers without pre-alignment or extensive manual configuration. The manual alignment process is extremely time-consuming and current automated solutions typically employ an infrared (IR) beam followed by an IR camera, which, besides increasing the transceiver cost, also requires an initial pre-convergence stage resorting to complementary coarse alignment technologies (e.g. Global Positioning System (GPS)). To tackle this challenge, we propose a novel methodology for the automatic alignment of FSO systems that does not require pre-convergence and avoids the use of costly IR cameras. The proposed alignment method is based on the application of computer vision (CV) during the transmission of a visible beacon and the utilization of pointing, acquisition and tracking (PAT) mechanisms. This solution is cost-effective, as the initial coarse alignment is carried out using visible light equipment, such as a standard CMOS camera and a visible beacon. Furthermore, it does not require any additional pre-convergence stage, since the alignment is based on characteristics acquired through CV during the transmission of the visible beacon, specifically the angle of inclination and the count of the number of pixels associated with the beacon. Additionally, the alignment process allows for a maximum angular misalignment of ±3.3 degrees between the optical antennas (OA), corresponding to a coverage area of $5.3 \text {m}^{2}$ at a distance of 20 meters. Finally, using this method, the successful alignment of an FSO system is demonstrated in a free-space link with 20 meters distance for different ambient light conditions, with real-time transmission at 16 Gbps.

Fiber-coupled free-space optics (FSO) communications have emerged as a promising wireless technology due to their flexibility, speed, security, and seamless integration with fiber optic systems. However, these systems are very sensitive to atmospheric conditions, particularly turbulence, necessitating robust and tailored solutions according to the application scenarios. However, the intrinsic random nature of atmospheric turbulence, together with the strong dependence on multiple external factors (e.g. varying weather conditions), makes it extremely challenging to adequately compare the merit of different turbulence mitigation techniques. In this work, resorting to the use of a custom-made atmospheric chamber, we tackle the issue of turbulence-induced power fading employing two complementary optical mitigation techniques: i) through enhanced fiber coupling efficiency using either standard single-mode fiber (SSMF) or multi-mode fiber (MMF) and ii) through tailored optical pre-amplification using either Erbium-doped fiber amplifiers (EDFAs) or semiconductor fiber amplifiers (SOAs). By carrying out a comprehensive set of repeatable and inter-comparable turbulence emulation tests, we demonstrate that MMF-based fiber coupling can be highly advantageous for less demanding FSO links, achieving 100% reliability after a real-time BER assessment at 4.5Gbps over weak-to-moderate turbulence, which represents a major improvement over the ~10-50% reliability obtained under the same circumstances for the SSMF-coupled system. In turn, for FSO links requiring high-capacity SSMF-coupled receivers, we demonstrate that EDFA-based pre-amplification operating either in saturation or automatic power control (APC) enabling 10 Gbps connectivity with 99% reliability in weak turbulence and ~96-98% in moderate turbulence regimes, in contrast with the baseline reliability of unamplified systems in the same turbulence conditions, which have shown

Abstract Background Preclinical studies highlight the importance of endogenous cannabinoids (endocannabinoids; eCBs) in neurodegeneration. Yet, prior observational studies focused on limited outcome measures and assessed only few eCB compounds while largely ignoring the complexity of the eCB system. We examined the associations of multiple circulating eCBs and eCB-like molecules with early markers of neurodegeneration and neuro-injury and tested for effect modification by sex. Methods This exploratory cross-sectional study included a random sample of 237 dementia-free older participants from the Framingham Heart Study Offspring cohort who attended examination cycle 9 (2011–2014), were 65 years or older, and cognitively healthy. Forty-four eCB compounds were quantified in serum, via liquid chromatography high-resolution mass spectrometry. Linear regression models were used to examine the associations of eCB levels with brain MRI measures (i.e., total cerebral brain volume, gray matter volume, hippocampal volume, and white matter hyperintensities volume) and blood biomarkers of Alzheimer’s disease and neuro-injury (i.e., total tau, neurofilament light, glial fibrillary acidic protein and Ubiquitin C-terminal hydrolase L1). All models were adjusted for potential confounders and effect modification by sex was examined. Results Participants mean age was 73.3 ± 6.2 years, and 40% were men. After adjustment for potential confounders and correction for multiple comparisons, no statistically significant associations were observed between eCB levels and the study outcomes. However, we identified multiple sex-specific associations between eCB levels and the various study outcomes. For example, high linoleoyl ethanolamide (LEA) levels were related to decreased hippocampal volume among men and to increased hippocampal volume among women (β ± SE = − 0.12 ± 0.06, p = 0.034 and β ± SE = 0.08 ± 0.04, p = 0.026, respectively). Conclusions Circulating eCBs may play a role in neuro-injury and may explain sex differences in susceptibility to accelerated brain aging. Particularly, our results highlight the possible involvement of eCBs from the N-acyl amino acids and fatty acid ethanolamide classes and suggest specific novel fatty acid compounds that may be implicated in brain aging. Furthermore, investigation of the eCBs contribution to neurodegenerative disease such as Alzheimer’s disease in humans is warranted, especially with prospective study designs and among diverse populations, including premenopausal women.

The evolving requirements of next-generation mobile communications networks can be met by leveraging vertically deployed Unmanned Aerial Vehicle (UAV) platforms integrated with Free Space Optical communications (FSO). This integration offers a flexible and scalable architecture capable of delivering high-rate communication without requiring licenses while aligning with the multi-gigabit paradigm. In recent times, the increasing availability of commercial aerial platforms has facilitated experimental demonstrations of UAV-enabled FSO systems, which play a crucial role in proposed backhaul networks and point-to-point communications by overcoming Line-of-Sight (LOS) challenges. These systems can be rapidly deployed to meet sudden demand scenarios. This document provides a comprehensive review of relevant field demonstrations of UAV-enabled FSO relay systems, with a particular focus on commercially available, free-flying platforms that are driving advancements in this domain. It categorizes the different platforms by considering the operational altitudes of these systems and their payload actuation capacity, which determines their adaptability to variables. The analysis aims to distill the design considerations that lead to optimal performance regarding communications throughput and other relevant metrics. Moreover, it also attempts to highlight areas where design choices have fallen short, indicating gaps in current research efforts toward the widespread adoption of UAV-enabled FSO relay systems. Finally, this work endeavors to outline effective design considerations, guidelines, and recommendations to bridge these identified gaps. It serves as a valuable reference guide for researchers involved in developing UAV-enabled FSO relay systems, enabling them to make informed decisions and pave the way for the successful implementation of such systems.

The use of medical cannabis (MC) to treat cancer-related symptoms is rising. However, there is a lack of long-term trials to assess the benefits and safety of MC treatment in this population. In this work, we followed up prospectively and longitudinally on the effectiveness and safety of MC treatment. Oncology patients reported on multiple symptoms before and after MC treatment initiation at one-, three-, and 6-month follow-ups. Oncologists reported on the patients' disease characteristics. Intention-to-treat models were used to assess changes in outcomes from baseline. MC treatment was initiated by 324 patients and 212, 158 and 126 reported at follow-ups. Most outcome measures improved significantly during MC treatment for most patients (p < 0.005). Specifically, at 6 months, total cancer symptoms burden declined from baseline by a median of 18%, from 122 (82–157) at baseline to 89 (45–138) at endpoint (−18.98; 95%CI= −26.95 to −11.00; p < 0.001). Reported adverse effects were common but mostly non-serious and remained stable during MC treatment. The results of this study suggest that MC treatment is generally safe for oncology patients and can potentially reduce the burden of associated symptoms with no serious MC-related adverse effects.

The continuous growth of Internet data traffic is pushing the current radio-frequency wireless technologies up to their physical limits. To overcome the upcoming bandwidth bottleneck, Free-Space Optics (FSO) is currently deemed as a key breakthrough toward next-generation ultra-high-capacity wireless links. Despite its numerous advantages, FSO also entails several particular challenges regarding the mitigation of the stochastic impairments induced by turbulence and the strict alignment requirements. One of the main issues of FSO communication systems is the mitigation of pointing errors and angle-of-arrival (AoA) fluctuations, which arise from misalignments induced by atmospheric turbulence and vibrations at the transmitting and receiving stations. A common approach to mitigate the impact of pointing errors is the use of an acquisition, tracking and pointing (ATP) system on one or both ends of the FSO link. In this paper, we present a characterization of the pointing errors and the AoA impact on the power budget of the FSO link to quantify the misalignment impairments. Afterwards, we experimentally demonstrate an FSO link with an ATP mechanism at both ends, managed by a control plane that enables the continuous and accurate alignment of the FSO link. To increase the misalignment tolerance, the ATP mechanism comprises two stages: the first one is based on a spatial diversity method provided by a quadrant detector, while the second stage maximizes the optical received power. Lastly, the impact of the beam misalignment on the achievable information rate of a coherent optical wireless system is theoretically addressed and characterized.

We propose and theoretically demonstrate an optically induced long-period gratings (OLPGs) based core switching technique for multi-core fibers (MCFs). This switching technique is fully reconfigurable in terms of signal wavelength and input–output fiber cores. The switching window and its efficiency can be adjusted by changing the peak power and the shape of the pump pulses, respectively. Switching efficiencies of 76% were found. Furthermore, we also show that the switched signal can be reshaped by tuning the shape of the pump pulses.

Introduction: Chronic non-cancer pain (CNCP) is one of the most prevalent indications for medical cannabis (MC) treatment globally. In this study, we investigated CNCP parameters in patients during prolonged MC treatment, and assessed the interrelation between CNCP parameters and the chemical composition of MC chemovar used.Methods: A cross-sectional questionnaire-based study was performed in one-month intervals for the duration of six months. Subjects were adult patients licensed for MC treatment who also reported a diagnosis of CNCP by a physician. Data included self-reported questionnaires. MC treatment features included administration route, cultivator, cultivar name and monthly dose. Comparison statistics were used to evaluate differences between the abovementioned parameters and the monthly MC chemovar doses at each time point.Results: 429, 150, 98, 71, 77 and 82 patients reported fully on their MC treatment regimens at six one-month intervals, respectively. Although pain intensities did not change during the study period, analgesic medication consumption rates decreased from 46 to 28% (p < 0.005) and good Quality of Life (QoL) rates increased from 49 to 62% (p < 0.05). These changes overlapped with increase in rates of (-)-Δ9-trans-tetrahydrocannabinol (THC) and α-pinene high dose consumption.Conclusion: Even though we observed that pain intensities did not improve during the study, QoL did improve and the rate of analgesic medication consumption decreased alongside with increasing rates of high dose THC and α-pinene consumption. Understanding MC treatment composition may shed light on its long-term effects.

The recovery of waste materials with potential for synthetic transformations is a major field in science. However, just few experiments have been devoted to undergraduate students by exploring some consistent subjects in light of simple, natural resources. Nucleophilicity is a central subject in chemistry and there are significant synthetic models to exploit it in contrast to basicity. Here we present a laboratory experiment that utilizes hands-on research to be implemented in an organic chemistry lab by using benzyl isothiocyanate (BITC) from papaya seeds as raw material for the preparation of thioureas in a fast and visually indicative experiment. Subjects such as green chemistry, extraction methods, nucleophilicity, chromatography and NMR spectroscopy can be emphasized in order to implement a project-based approach. This experiment shows flexibility concerning the procedures and the use of biomass raw materials towards the reinforcement of a research-like experience and critical-thinking skills.

Abstract Background The cumulus expansion process is one of the LH mediated ovulatory processes. Hyaluronan synthase 2 (HAS2) regulates the synthesis of hyaluronic acid, the main component of the cumulus expansion process. Recently, the lncRNA HAS2 antisense RNA 1 (HAS2-AS1) was identified in our global transcriptome RNA-sequencing of novel ovulation associated genes. The role of HAS2-AS1 in HAS2 regulation w.as studied previously with contradictive results in different models but not in the ovary. Taken together the induction of HAS2-AS1 and the important role of HAS2 in the cumulus expansion process, we hypothesize that HAS2-AS1 regulate HAS2 expression and function in the ovary. Therefore we undertook to study the expression, regulation, and possible functional role of HAS2-AS1 in the human ovary. Results HAS2-AS1, located within the HAS2 gene that was highly regulated in our library. We found that HAS2-AS1 express mainly in cumulus cells (CCs). Furthermore, HAS2-AS1 showed low expression in immature CCs and a significant increase expression in mature CCs. Functional studies reveal that inhibition of HAS2-AS1 by siRNA caused decrease expression of HAS2. Furthermore, inhibition of HAS2-AS1 by siRNA results in decrease migration of granulosa cells. Conclusions Our results suggest that HAS2-AS1 is an LH/hCG target gene that plays a positive role in HAS2 expression and thus might play a role in regulating cumulus expansion and migration.

Actinomycetes are one of the most important groups of soil bacteria that are recognized as sources of commercially important enzymes and antimicrobials. Actinomycetes, however, are largely underestimated and uncharacterized in underexplored habitats such as green spaces in urban areas. This study aimed to isolate actinomycetes from soils in the University of the Philippines Diliman campus and determine their cellulolytic and antimicrobial activities. A total of 235 isolates were purified from the soil samples collected. Cellulolytic and antimicrobial activities were observed in 114 and 18 isolates, respectively. The cell-free supernatants of 31 isolates exhibited high cellulolytic activities. Two isolates, in particular EWLG2 and EPNA9, had 0.596 FPU and 0.885 FPU cellulolytic activity, respectively. Seven isolates exhibited antimicrobial activities in the screening methods used. The crude extracts of isolates AWLG9, AWLG8, AWLG10, AULG1, APLG2, and AWLG13 had minimum inhibitory concentrations (MIC) values ranging from 31.25 µg/mL to 500 µg/mL against Candida spp. Isolates AULG1 and EPLG5 were active against the bacterial test microorganisms and had MIC values ranging from 250 µg/mL to 500 µg/mL. DNA sequencing identified the isolates which exhibited high cellulolytic and antimicrobial activities as Bacillus sp. and Streptomyces sp., with percent identities ≥98%. This study shows that green spaces are rich sources of soil microorganisms that have cellulolytic and antimicrobial activities. It is recommended that the isolates obtained in this study be examined further for possible applications in bioethanol production and pharmacology.

Abstract Background Bloom syndrome (BS) is a rare autosomal recessive chromosome instability disorder. The main clinical manifestations are growth deficiency, telangiectasic facial erythema, immunodeficiency, and increased risk to develop neoplasias at early age. Cytogenetic test for sister chromatid exchanges (SCEs) is used as a diagnostic marker for BS. In addition, most patients also present mutations in the BLM gene, related to defects in the DNA repair mechanism. However, the molecular mechanism behind the pathogenicity of BS is still not completely understood. Methods We describe two patients confirmed with BS by SCE and molecular analysis. Also, we performed the gene expression profile by the RNA‐seq methodology in mRNA transcripts for differential gene expression analysis using as a biological condition for comparison BS versus health controls. Results We detected 216 differentially expressed genes related to immunological pathways such as positive regulation and activation of B cells, immune effector process and absence of difference of DNA repair genes expression. In addition; we also observed differentially expressed genes associated with apoptosis control, such as BCL2L1, CASP7, CDKN1A, E2F2, ITPR, CD274, TNFAIP6, TNFRSF25, TNFRSF13C, and TNFRSF17. Conclusion Our results suggest that the combination of altered expression of genes involved in signaling pathways of immune response and apoptosis control may contribute directly to the main characteristics observed in BS, such as recurrent infections, growth failure, and high risk of cancer. Transcriptome studies of other instability syndromes could allow a more accurate analysis of the relevant gene interactions associated with the destabilization of the genome. This is a first description of the profile of differential gene expression related to immunological aspects detected in patients with BS by RNA‐seq.

Abstract Background Cri du chat syndrome (CdCS) is a rare syndrome caused by a partial or complete deletion of the short arm of chromosome 5 (5p‐). The main clinical features include a high‐pitched cry, facial asymmetry, microcephaly, round face at birth, epicanthal folds, hypotonia, delayed growth and development. Methods We studied 14 Brazilian patients with CdCS using genomic array in order to better define the 5p breakpoints and recognize copy number variations (CNVs) that contribute to clinical manifestations associated with the syndrome. Results Array confirmed terminal deletions in 13 patients and an interstitial deletion in one patient. It was also possible to map the breakpoints and associate a genomic region of 4.7 Mb to the development of head circumference and cat‐like cry. We also found other CNVs concomitant to the 5p deletion including a 9p duplication, a 17q deletion, and a 22q deletion in three different patients. Conclusion With advancements of molecular cytogenomic methods in the last two decades, it was possible to evidence cryptic alterations and improve the genotype–phenotype correlation. In this work, we describe a new genomic region associated with microcephaly and cat‐like cry and highlight the importance of precise delineation of 5p deletion breakpoints and detection of other CNVs in CdCS patients to improve genotype–phenotype correlation to perform a complete clinical and molecular diagnosis.

Objective The aim of this cross-sectional questionnaire-based study was to identify associations between the doses of cannabinoids and terpenes administered, and symptoms of attention deficit hyperactivity disorder (ADHD). Methods Participants were adult patients licensed for medical cannabis (MC) treatment who also reported a diagnosis of ADHD by a physician. Data on demographics, ADHD, sleep, and anxiety were collected using self-report questionnaires. Data collected on MC treatment included administration route, cultivator, cultivar name, and monthly dose. Comparison statistics were used to evaluate differences in reported parameters between low (20–30 g, n=18) and high (40–70 g, n=35) MC monthly dose and low adult ADHD self-report scale (ASRS, 0–5) score (i.e. ≤3.17 score, n=30) or high ASRS score (i.e. ≥3.18 score, n=29) subgroups. Results From the 59 patients that answered the questionnaire, MC chemovar could be calculated for 27 (45%) of them. The high MC monthly dose group consumed higher levels of most phyto-cannabinoids and terpenes, but that was not the case for all of the cannabis components. The high dose consumers and the ones with lower ASRS score reported a higher occurrence of stopping all ADHD medications. Moreover, there was an association between lower ASRS score subgroup and lower anxiety scores. In addition, we found an association between lower ASRS score and consumption of high doses of cannabinol (CBN), but not with Δ-9-tetrahydrocannabinol (THC). Conclusion These findings reveal that the higher-dose consumption of MC components (phyto-cannabinoids and terpenes) is associated with ADHD medication reduction. In addition, high dosage of CBN was associated with a lower ASRS score. However, more studies are needed in order to fully understand if cannabis and its constituents can be used for management of ADHD.

Staphylococcus aureus is a Gram-positive bacterium that causes minor skin infections to life-threatening diseases. It is transmitted through direct contact with fomites, such as computer peripherals and handrails. Treatment of S. aureus infections is generally straightforward, but is complicated by drug-resistant strains, particularly methicillin-resistant S. aureus (MRSA). The University of the Philippines Diliman (UP Diliman) has hundreds of computer service providers (CSPs) and public utility jeepneys (PUJs) regularly used by faculty, students, staff, and visitors. While no outbreaks of S. aureus and MRSA have been reported, the possibility of infection with this pathogen through CSPs and PUJs is very likely. The objectives of this study are to determine the carriage rates of S. aureus and MRSA in CSPs, computer peripherals, and handrails of PUJs inside UP Diliman, and to identify the risk factors associated with S. aureus and MRSA contamination. A total of 162 computer peripherals from 27 CSPs and 196 PUJ handrails were swabbed. S. aureus isolates were identified using colony morphology, biochemical tests, and amplification of the nuc gene, whereas MRSA isolates were identified using the cefoxitin challenge and amplification of the mecA gene. S. aureus was identified in 92.6% of CSPs, 36.4% of computer peripherals, and 7.1% of PUJs, while MRSA carriage was 3.1% in CSPs and 2% in PUJs. No signif icant associations between S. aureus/MRSA and the assessed risk factors were observed (p > 0.05). Results indicate that while S. aureus prevalence is relatively high, MRSA carriage is low in CSPs and PUJs in UP Diliman.

Nuria Bruguera-Avila,1–3 Alicia Marin,3–5 Ignasi Garcia-Olive,3–5 Joaquim Radua,6–8 Cristina Prat,4,9,10 Montserrat Gil,3 Juan Ruiz-Manzano2–5 1Department of Medicine, Hospital Sant Jaume de Calella, Calella, Barcelona, Spain; 2Department of Medicine, Universitat Autònoma de Barcelona, Bellatera, Spain; 3Department of Pulmonary Medicine, Hospital Universitari Germans Trias i Pujol, Carretera del Canyet sn, Badalona, Barcelona, Spain; 4Ciber de Enfermedades Respiratorias, Instituto de Salud Carlos III, Madrid, Spain; 5Fundació Institut d’Investigació en Ciències de la Salut Germans Trias i Pujol, Carretera del Canyet sn, Badalona, Barcelona, Spain; 6Department of Statistics, FIDMAG Germanes Hospitalaries Research Unit, Sant Boi de Llobregat, Barcelona, Spain; 7CiberSam – Ciber de Salud Mental, Madrid, Spain; 8Centre for Psychiatry Research, Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden; 9Department of Microbiology, Hospital Universitari Germans Trias i Pujol, Carretera del Canyet sn, Badalona, Barcelona, Spain; 10Department of Genetics and Microbiology of Universitat Autònoma de Barcelona, Bellatera, Spain Objectives: To analyze whether the introduction of nebulized colistin in patients with chronic obstructive pulmonary disease (COPD) and infection with Pseudomonas aeruginosa (PA) is associated with a decrease of the number and duration of severe exacerbations.Materials and methods: Thirty six patients with COPD and infection with PA treated with nebulized colistin attending a day hospital during a 5-year (January 2010–December 2014) period were prospectively included. Repeated-measures t-tests were used to assess whether the introduction of colistin was associated with changes in the number of exacerbations or the length of the hospitalizations, comparing for each patient the year prior to the introduction of colistin with the year after.Results: After the introduction of colistin, the number of admissions decreased from 2.0 to 0.9 per individual year (P=0.0007), and hospitalizations were shorter (23.3 vs 10.9 days, P=0.00005). These results persisted when patients with and without bronchiectasis or with and without persistence of Pseudomonas were separately analyzed. No pre–post differences were detected in the number of exacerbations not requiring admission.Conclusion: Nebulized colistin seems associated with a strong decrease in the number and duration of hospitalizations due to exacerbation in patients with COPD and infection with PA. Clinical trials with a larger number of patients are needed in order to confirm these results. Keywords: bronchiectasis, colistin, COPD, nebulized antibiotics

In the last decade the use of medical cannabis (MC) for palliative cancer treatment has risen. However, the choice between products is arbitrary and most patients are using Tetrahydrocannabinol (THC)-dominant cannabis products. In this study, we aimed to assess the short-term outcomes of MC treatment prescribed by oncologists in relation to the type of cannabis they receive. A comparative analysis was used to assess the differences in treatment effectiveness and safety between THC-dominant (n = 56, 52%), cannabidiol (CBD)-dominant (n = 19, 18%), and mixed (n = 33, 30%) MC treatments. Oncology patients (n = 108) reported on multiple symptoms in baseline questionnaires, initiated MC treatment, and completed a one-month follow-up. Most parameters improved significantly from baseline, including pain intensity, affective and sensory pain, sleep quality and duration, cancer distress, and both physical and psychological symptom burden. There was no significant difference between the three MC treatments in the MC-related safety profile. Generally, there were no differences between the three MC treatments in pain intensity and in most secondary outcomes. Unexpectedly, CBD-dominant oil treatments were similar to THC-dominant treatments in their beneficial effects for most secondary outcomes. THC-dominant treatments showed significant superiority in their beneficial effect only in sleep duration compared to CBD-dominant treatments. This work provides evidence that, though patients usually consume THC-dominant products, caregivers should also consider CBD-dominant products as a useful treatment for cancer-related symptoms.

Background: Medical cannabis (MC) treatment for migraine is practically emerging, although sufficient clinical data are not available for this indication. This cross-sectional questionnaire-based study aimed to investigate the associations between phytocannabinoid treatment and migraine frequency. Methods: Participants were migraine patients licensed for MC treatment. Data included self-reported questionnaires and MC treatment features. Patients were retrospectively classified as responders vs. non-responders (≥50% vs. n = 89, 61%) reported lower current migraine disability and lower negative impact, and lower rates of opioid and triptan consumption. Subgroup analysis demonstrated that responders consumed higher doses of the phytocannabinoid ms_373_15c and lower doses of the phytocannabinoid ms_331_18d (3.40 95% CI (1.10 to 12.00); p < 0.01 and 0.22 95% CI (0.05–0.72); p < 0.05, respectively). Conclusions: These findings indicate that MC results in long-term reduction of migraine frequency in >60% of treated patients and is associated with less disability and lower antimigraine medication intake. They also point to the MC composition, which may be potentially efficacious in migraine patients.

Sunflower is a pollinator-dependent crop and one of the most cultivated oilseeds in the world, supporting important sectors of the agricultural industry, such as the food supply, because it is an important source of vitamin E and unsaturated fatty acids for human health. Although it is well stablished that bee pollination improves sunflower seed set, it is still unknown if pollinators influence the nutritional composition. Considering the economic importance of sunflowers for several Brazilian agricultural sectors, the aim of this study was to evaluate the effect of the bee community for (1) achene quality (weight and nutritional composition) and (2) market value. Exclusion experiments were performed with hybrid sunflowers and showed that bee pollination enhanced the achene weight by 91 %, the levels of vitamin E by 45 % and unsaturated fatty acids by 0.3 %. Also, it was estimated that due to the pollination services provided by bees, the grower of the sunflower cultivar used in this study nearly duplicates the sale value of the achenes per hectare of cultivated area. Thus, the current study highlights the importance of bees as providers of cross- and self-pollination to nutritional quality of sunflower achenes and provides useful baseline figures to further evaluations of the effects of pollinators on human diets and health.

Toxoplasma gondii is a protozoan parasite that causes toxoplasmosis. It is widespread in the environment and infects a variety of warm-blooded animals, causing miscarriages and birth problems. Previous studies in the Philippines have determined the seropositivity of T. gondii in humans. However, the seroprevalence of the parasite among household pets, par ticularly its feline def initive host, remains insufficient . This study aimed to: (1) determine the seroprevalence of T. gondii antibodies among domestic and stray cats in the Philippines; and, (2) to analyze the risk factors associated with seropositivity. Blood samples from 59 domestic and stray cats were collected and tested for T. gondii seropositivity using a commercially available indirect ELISA kit, while pet owners and handlers were given questionnaires about their cats. Thirteen or 22.03% of the cats were seropositive to T. gondii, and risk factor analysis revealed a significant difference between domestic and stray cats with regard to diet (p = 0.026, OR = 8.333, c = 0.299) and domestication (p = 0.039, OR = 5.000, c = 0.276). Cats fed with table food tested 31.43% seropositive compared to the 4.35% of those fed with cat food, whereas 33.33% of the stray cats were seropositive compared to 7.69% for domestic cats. Odds ratio test showed that the risk factors studied were associated with higher likelihood of T. gondii seropositivity. These results implicate diet and environment in the transmission dynamics of T. gondii among cats.

Objective: This report aims to describe unique manifestations of proboscis lateralis and highlight the importance of a multidisciplinary approach to address the problems that arise from this rare congenital anomaly. Methods: Study Design: Case Report Setting: Tertiary Government Hospital Patient: One Results: A 13 year-old girl diagnosed with proboscis lateralis presented with a trunk-like appendage projecting from the surface of the right supramedial canthal area. She also had clear nasal discharge, nasal congestion, mouth-breathing, and snoring since birth. Paranasal Sinus (PNS) CT scan with 3D reconstruction showed agenesis of the right paranasal sinuses, and expansile aeration of the left paranasal sinuses. Due to her condition, the drainage system of the paranasal sinuses was obstructed, causing chronic rhinosinusitis (CRS). This hindered plans for reconstructive surgery despite medical management, hence the patient underwent Endoscopic Sinus Surgery (ESS). Conclusion: Proboscis lateralis is a rare congenital anomaly that results in aesthetic problems as well as airway concerns, such as rhinosinusitis and obstructive sleep apnea syndrome (OSAS). Management entails a multidisciplinary approach to address functional and aesthetic problems of the patient. Keywords: proboscis lateralis, chronic rhinosinusitis, obstructive sleep apnea, endoscopic sinus surgery, multidisciplinary approach, plastic surgery, reconstructive surgery

Objective: To describe a 2-year old boy with true congenital macroglossia surgically managed using a modified Kole technique. Methods: Study Design: Surgical Innovation Setting: Tertiary Government Hospital Patient: One Results: A 2-year-old boy presented with congenital macroglossia, associated with difficulty feeding and phonating. On physical examination, the massive tongue had both increased length and width. At rest, it protruded between the upper and lower teeth, with drying and fissuring of the tip. Dribbling of saliva and mandible prognathism were also noted. The child was surgically treated with a modified Kole technique, wherein the apex of the anterior wedge resection was extended to the posterior third midline. Final histopathology was consistent with cavernous hemangioma. Conclusion: The modified Kole technique proved viable, as the postoperative results were considered satisfactory. Tongue volume was uniformly reduced in length and width, enabling mouth and jaw closure, while tongue sensation and mobility were preserved. Feeding, speech intelligibility and cosmesis were markedly improved. Future application of this modification may prove its usefulness. Keywords: macroglossia; glossectomy; congenital macroglossia

Acanthamoeba spp. are opportunistic pathogens that cause amebic keratitis and granulomatous amebic encephalitis in man. Recent attempts to correlate pathogenicity with species have been proven difficult due to inconsistencies in morphology-based classification. The objectives of this study were: (1) to compare clinical and environmental isolates based on morphology, protease and gelatinase activity, and the cysteine proteinase (CP) gene, and (2) to determine whether these features can be used to differentiate the isolates. Results show some degree of variation in trophozoite and cyst morphology. Zymography, demonstrated gross differences in banding patterns, and the protease activity of clinical isolates was greater than the environmental isolates (p-value < 0.01). Amplification of the CP gene yielded two bands in the environmental isolates, approximately 755 bp and 440 bp in length. In contrast, only one band, either the 755 bp or 440 bp band was amplified in the clinical isolates. The results confirmed the limitations of morphology in differentiating Acanthamoeba species, and suggest that zymography, protease activity, and detection of the CP gene are useful reference tests to distinguish pathogenic from non-pathogenic isolates.

Antimicrobial chemotherapy is critical in the fight against infectious diseases caused by Entamoeba histolytica. Among the drugs available for the treatment of amebiasis, metronidazole (MTZ) is considered the drug of choice. Recently, in vitro studies have described MTZ resistance and the potential mechanisms involved. Costs to fitness and adaptive responses associated with resistance, however, have not been investigated. In this study we generated an HM-1 derived strain resistant to 12 µM MTZ (MTZR). We examined its phenotypic and transcriptional profile to determine the consequences and mRNA level changes associated with MTZ resistance. Our results indicated increased cell size and granularity, and decreased rates in cell division, adhesion, phagocytosis, cytopathogenicity, and glucose consumption. Transcriptome analysis revealed 142 differentially expressed genes in MTZR. In contrast to other MTZ resistant parasites, MTZR did not down-regulate pyruvate:ferredoxin oxidoreductase, but showed increased expression of genes for a hypothetical protein (HP1) and several iron-sulfur flavoproteins, and downregulation of genes for leucine-rich proteins. Fisher’s exact test showed 24 significantly enriched GO terms in MTZR, and a 3-way comparison of modulated genes in MTZR against those of MTZR cultured without MTZ and HM-1 cultured with MTZ, showed that 88 genes were specific to MTZR. Overall, our findings suggested that MTZ resistance is associated with specific transcriptional changes and decreased parasite virulence.

BackgroundPreclinical studies highlight the importance of endogenous cannabinoids (endocannabinoids; eCBs) in neurodegeneration. Yet, prior observational studies focused on limited outcome measures and assessed only few eCB compounds while largely ignoring the complexity of the eCB system. We examined the associations of multiple circulating eCBs and eCB-like molecules with early markers of neurodegeneration and neuro-injury and tested for effect modification by sex.MethodsThis exploratory cross-sectional study included a random sample of 237 dementia-free older participants from the Framingham Heart Study Offspring cohort who attended examination cycle 9 (2011-2014), were 65 years or older, and cognitively healthy. Forty-four eCB compounds were quantified in serum, via liquid chromatography high-resolution mass spectrometry. Linear regression models were used to examine the associations of eCB levels with brain MRI measures (i.e., total cerebral brain volume, gray matter volume, hippocampal volume, and white matter hyperintensities volume) and blood biomarkers of Alzheimer's disease and neuro-injury (i.e., total tau, neurofilament light, glial fibrillary acidic protein and Ubiquitin C-terminal hydrolase L1). All models were adjusted for potential confounders and effect modification by sex was examined.ResultsParticipants mean age was 73.3 ± 6.2 years, and 40% were men. After adjustment for potential confounders and correction for multiple comparisons, no statistically significant associations were observed between eCB levels and the study outcomes. However, we identified multiple sex-specific associations between eCB levels and the various study outcomes. For example, high linoleoyl ethanolamide (LEA) levels were related to decreased hippocampal volume among men and to increased hippocampal volume among women (β ± SE =  - 0.12 ± 0.06, p = 0.034 and β ± SE = 0.08 ± 0.04, p = 0.026, respectively).ConclusionsCirculating eCBs may play a role in neuro-injury and may explain sex differences in susceptibility to accelerated brain aging. Particularly, our results highlight the possible involvement of eCBs from the N-acyl amino acids and fatty acid ethanolamide classes and suggest specific novel fatty acid compounds that may be implicated in brain aging. Furthermore, investigation of the eCBs contribution to neurodegenerative disease such as Alzheimer's disease in humans is warranted, especially with prospective study designs and among diverse populations, including premenopausal women.

Met-hepatocyte growth factorlscatter factor (HGFJSF) signaling plays an important role in epithelial tissue morphogenesis, lumen formation, tumorigenicity. We have recently demonstrated that HGFJSF also alters the metabolic activity of cells by enhancing both the glycolytic and oxidative phosphorylation pathways of energy production. Using differential display polymerase chain reaction, we cloned a novel gene, designated mimp (Met-Induced Mitochondrial Protein), which is upregulated in NIH-3T3 cells cotransfected with both HGFISFand Met (HMH cells). Northern and Western blot analyses showed that mime is induced in several Metexpressing cell lines following treatment with HGFJSF. Mimp encodes a 33-kDa protein that shows sequence homology to the family of mitochondrial carrier proteins (MCPs). Murine Mimp (mMimp) is expressed in a wide variety of tissues., exhibiting an expression pattern similar to Met. Predominant expression is seen in liver, kidney, heart, skeletal muscle, testis. Using immunostaining for HA-tagged mMimp and a GFP-mMimp chimeric protein as well as subcellular fractionation, we determined that Mimp is primarily localized to the mitochondria. Ectopic expression of mMimp in the Met-responsive adenocarcinoma cell line, DA3, reduced the mitochondrial membrane potential (uncoupling activity). The extent of the mitochondrial depolarization positively correlated with the level of Mimp expression. Our results demonstrate that Mimp is a novel mitochondrial carrier homologue upregulated by Met-HGFJSF signal transduction, which leads to mitochondrial depolarization, suggest novel links among tyrosine kinase signaling, mitochondrial function, cellular bmenergetics.

OBJECTIVE: To investigate the mRNA expression of genes related to steroidogenesis and OHSS in granulosa cells (GCs) of patients triggered with GnRH agonist compared to patients triggered with hCG. DESIGN: Mural GCs were obtained at the time of oocyte retrieval and gene expression was analyzed using quantitative real time RT-PCR. SETTINGS: Single center, case control study. PATIENT(S): 24 women who were treated with GnRH agonist or hCG for triggering of ovulation. INTERVENTIONS: GC collection. MAIN OUTCOME MEASURE(S): The expression of genes related to steroidogenesis and OHSS in mural GCs. RESULTS: The fertilization rate was similar in the two groups. The mRNA expression of CYP19A1 (0.50 vs 1, arbitrary unit), CYP11A1 (0.6 vs. 1) and 3 beta hydroxysteroid-dehydrogenase (0.39 vs 1) was significantly lower in the GnRH group. The expression of VEGF (0.74 vs. 1) and inhibin β B (0.38 vs 1) was lower in the GnRH analog triggered group. CONCLUSION: Expression of genes related to steroidogenesis is lower at the time of oocyte retrieval in patients triggered with GnRH agonist. The decreased expression of VEGF and inhibin β B in the GnRH agonist group can explain the mechanism of early OHSS prevention.