2-week Intervals Research Articles

Reliability and Validity Study of the Migraine Interictal Burden Scale-4 in Turkish

ABSTRACT Objective: The objective of this study was to assess the reliability and validity of the Turkish version of the Migraine Interictal Burden Scale-4 (MIBS-4) in patients with migraine. MIBS-4 measures migraine-related interictal burden in four domains related to difficulty in planning at work or school, family and social life, and emotional/affective and cognitive stress. Materials and Methods: A total of 178 patients with migraine were enrolled in this multicenter, prospective study in two consecutive interviews with 4-week intervals. The comprehensibility, patient–physician reliability, internal consistency, test–retest reliability, and validity of the Turkish translation of MIBS-4 were analyzed. Results: In terms of comprehensibility of all MIBS-4 questions, a statistically significant agreement was obtained between the patient and the physician (intraclass correlation coefficient [ICC] = 0.713; P < 0.001, ICC = 0.851; P < 0.001, ICC = 0.637; and P < 0.001, ICC = 0.760; P < 0.001). No statistically significant difference was found between the comprehensibility of the first, second, third, and fourth questions of MIBS-4 according to the patient self-test and the physician interviews (P = 0.167, P = 0.068, P = 0.121, and P = 0.225, respectively). A significant high consistency was obtained between the first and second interview values (ICC = 0.891; P < 0.001). Cronbach’s alpha coefficient was obtained between 0.818 and 0.845, and the scale was obtained with high reliability. A statistically significant positive correlation was obtained between the first and second interview MIBS values and Headache Impact Test-6, and the correlation coefficients were obtained as 0.158 and 0.330, respectively (P = 0.036 and P < 0.001, respectively). Conclusion: These results demonstrated that the Turkish translation of MIBS-4 is equivalent to the English version in terms of internal consistency, and it has high test–retest reliability and validity. The Turkish version of MIBS-4 can serve as a reliable, useful, and valid tool for assessing the burden on patients between migraine attacks, as well as aiding health-care professionals in enhancing migraine treatment strategies in Türkiye.

Anti-IL17 Secukinumab in hidradenitis suppurativa: A long-term drug survival analysis.

Real-world data on the long-term effectiveness of the anti-IL17 agent secukinumab in treating moderate-to-severe Hidradenitis suppurativa (HS) are lacking. In this study, 24 patients with moderate-severe HS received five weekly subcutaneous injections followed by maintenance doses every 4 weeks. Primary outcomes included HiSCR, IHS4 reduction, and DLQI measures assessed at 12-week intervals. The median secukinumab drug survival was 16.0 months (range 3-51), with a 56.5% maximal response rate at 6 months and dropout exceeding 40% at 1 year. Baseline disease burden emerged as a key predictor of treatment response, overshadowing factors like sex or BMI. Prior systemic steroid use negatively impacts drug survival. The study underscores the critical 6-month window for assessing treatment efficacy, emphasizing the importance of initial induction dosing. Additionally, the newly developed scoring system, IHS4-55, showed analogies to the older HiSCR score in capturing treatment response. In this real-life scenario, challenges persist in HS management, necessitating innovative therapeutic approaches and predictive markers.

Bacterial Contamination and Antimicrobial Resistance in Two-Spotted (Gryllus bimaculatus) and House (Acheta domesticus) Cricket Rearing and Harvesting Processes.

Food safety for cricket production is a crucial factor in producing edible crickets with safety for consumers and sustainability for two-spotted (Gryllus bimaculatus) as well as house (Acheta domesticus) cricket production. This study was conducted by simultaneously rearing two cricket species, comprising two-spotted crickets (G. bimaculatus) and house crickets (A. domesticus). A total of 16 rearing crates were used for the present study, which were allocated into 8 rearing crates for each studied cricket species, including paper egg cartons. Cricket eggs were incubated in the rearing crates. Once the crickets hatched, tap water and powdered feed were provided ad libitum throughout the experiment. At the end of this study (35 and 42 days for the two-spotted and house crickets, respectively), all crickets were harvested, rinsed in tap water, and boiled in water for 5 min. During the rearing and harvesting processes, samples were collected from various potential contamination points for bacteria, including E. coli and Salmonella spp. There were samples of the initial input (feed, drinking water, and staff hands), rearing environment (water pipe, crate wall, living cartons, frass, and cricket surface), and harvesting crickets (harvested, washed, and boiled crickets), with a 2-week sampling interval, except for the last round of sampling for the two-spotted crickets. Subsequently, all samples were submitted to isolate and identify contaminated bacteria. The samples from the last round of sampling for both kinds of crickets were submitted to quantify the level of contamination for E. coli and Salmonella spp., including antimicrobial resistance by the disk diffusion method for the positive isolate. The results showed that bacterial contamination was found in the rearing of both cricket species, primarily involving Klebsiella spp. and Enterobacter spp., mainly found in prepared drinking water and the water pipes of drinking water supply equipment, which are potential sources of contamination with cricket frass. E. coli was found in 4.8% and 4.3% of the two-spotted and house crickets, respectively, while no presence of Salmonella spp. was detected in any submitted samples. The quantification of E. coli and Salmonella spp. indicated E. coli contamination near the water pipe and the frass of two-spotted crickets, but Salmonella spp. was undetectable in both two-spotted and house crickets. The antimicrobial resistance of isolated E. coli mainly involved penicillin G, amoxicillin, ampicillin, erythromycin, lincomycin, and tiamulin. Thus, good farm management with proper sanitation practices (such as cleaning and keeping the environment dry), as well as boiling crickets during the harvesting process, may help ensure the safety of edible cricket production.

Treatment of myofascial pain and dysfunction using botulinum toxin A: a prospective study

Abstract Purpose We prospectively assessed the effects of botulinum toxin type-A (BTX-A) on primary and secondary outcomes in a population of refractory myofascial pain and dysfunction patients when conservative management had proven ineffective. Methods In this study, 26 patients with masticatory myofascial pain, who were refractory to conservative management, were enrolled prospectively to evaluate responses following the injection of botulinum toxin-A (BTX-A). Masseter muscles were injected with 30 units BTX-A and 20 units into the temporalis muscles. Pain, tenderness to palpation, and oral function were evaluated subjectively using a visual analog scale (VAS). Objective outcomes of maximal mouth opening (MMO) and reduction in total facial width after injection with BTX-A were measured. Participants were reassessed at 1-week, 1, 3, and 6-month intervals. A linear mixed-effect model was employed to assess the level of correlation (dependence) among different outcomes. Results Administration of BTX-A had a significant strong positive correlation with the reduction of pain (Phi = 0.641, P < 0.0005); significant strong positive correlation with increase in oral function (Phi = 0.738, P < 0.0015); significant strong positive correlation with increase in maximal mouth opening (Phi = 0.645, P < 0.0085); significant strong positive correlation with tenderness to palpation (Phi = 0.510, P < 0.0011); and significant strong positive correlation with reduction in facial width (Phi = 0.565, P < 0.0001). Conclusion The results from this study demonstrate that BTX-A administration may provide a safe and effective means to treat myofascial pain from hyperfunctioning masticatory muscles. It is not recommended to replace first-line treatment but may provide relief from chronic facial pain if properly administered in patients where standard conservative management has been unsuccessful.

Real-World 1-Year Outcomes of Treatment-Intensive Neovascular Age-Related Macular Degeneration Switched to Faricimab

PurposeTo report one-year anatomical and functional real-world outcomes of treatment intensive neovascular age related macular degeneration (nAMD) patients switched to faricimab DesignRetrospective multi-centre cohort study SubjectsConsecutive nAMD patients on 4-weekly treatment interval with either ranibizumab or aflibercept 2mg in the last three visits within a treat and extend protocol (high treatment burden) prior to switch to faricimab at Moorfields Eye Hospital between 5/9/2022- 5/12/2022. MethodsTotal number of nAMD patients switched to faricimab were identified from electronic medical records and those who met criteria of high treatment burden were included. Data collected included pre and post-switch visual acuity (VA), treatment intervals, length of follow-up, baseline macular morphology, changes in central subfield thickness (CST), macular fluid status and adverse events. Main outcome measuresVA, CST, presence of intraretinal fluid (IRF), subretinal fluid (SRF) and injection intervals over one-year following switch to faricimab. ResultsA total of 130/ 286 (45.5%) eyes met inclusion criteria of being switched due to high treatment burden and 117 were included in analysis. Prior to switch to faricimab, these eyes received mean total number of injections of 33.4±19.6 over mean of 51.3±34.9 months. Mean number of injections in 12 months preceding switch was 10.1±1.6 and mean interval of the preceding three injections was 4.2±0.3 weeks. Mean VA, CST and percentage of patients with dry macula prior to switch were 66.0±11.9 ETDRS letters, 259.6±76.0μm and 18.3% respectively. Following switch, there was no statistical difference in mean VA after each visit and at 12 months. Mean CST statistically significantly reduced following the 3rd faricimab injection and at 12 months by 20.0μm (p=0.035) and 22.1μm (p=0.041) respectively. Mean treatment intervals increased to 6.9±2.3 weeks (p<0.005) at 12 months with 42.9% and 11.4% of patients being on ≥8 weekly and ≥12 weekly treatment intervals respectively. ConclusionAt 12 months, patients with nAMD with previous record of high treatment burden when switched to faricimab maintained visual acuities and improved anatomical outcomes on extended treatment intervals. Physician bias is inherent in these types of observational studies so a prospective randomised controlled trial is recommended to validate these findings.

Impact of sub chronic administration of deltamethrin on autoimmune activity in rat

Deltamethrin (DLM) is a newer kind of insecticide that is used on pets, livestock, and crops, as well as to combat malaria vectors and household pests. It belongs to the synthetic pyrethroid group and is being promoted as an alternative to organophosphate chemicals due to its persistent and destructive effects. The current study aimed to evaluate the impact of sub-chronic oral exposure to DLM on autoimmune activity in rats. Three groups of male albino rats (15 rats/group) including the control group, the ethanol-treated group (1 ml/rat), and the DLM-treated group (5 mg/kg b.w). Samples of blood were taken from all groups at 4-, 8- and 12-week intervals for the determination of hematological, cytokines, and immunological parameters. T lymphocyte subsets and Treg lymphocytes were determined in serum using flow cytometric acquisition. The results revealed that DLM significantly increased TNF-α, IL-33, IL-6, IL-17, IgG, IgM, WBCs, differential count, and platelets while decreasing Hb concentration and RBCs. Additionally, DLM decreased the number of T-cell subsets (CD3, CD4, CD5, and CD8) and Treg lymphocytes. All of these impacts became more severe over time. It is possible to conclude that the sub-chronic oral exposure to DLM disturbed autoimmune activity through the disturbances in immunological indices, CDs subset Treg lymphocytes.

Management of Idiopathic Sudden Sensorineural Hearing Loss (ISSNHL) Intratympanic Platelet-Rich Plasma (PRP) Versus Intratympanic Steroid Injections: A Cross-Sectional Study

&lt;b&gt;&lt;br&gt;Introduction:&lt;/b&gt; Idiopathic sensorineural hearing loss of 30 decibels (dB) or more over at least three contiguous audiometric frequencies with an onset of less than 3 days is referred to as sudden sensorineural hearing loss (ISSNHL) and is known as an ENT (ear, nose, and throat) emergency. When a patient’s hearing suddenly deteriorates, they become confused, anxious, and worried. One of the primary therapies for sudden sensorineural hearing loss is intratympanic steroids. Intratympanic injections of platelet-rich plasma (PRP) improve inner ear hair cells, which enhances hearing.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Aim:&lt;/b&gt; To show the safety and efficacy of intratympanic PRP injection in the management of ISSNHL in comparison with intratympanic steroid injection.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Methods:&lt;/b&gt; The study group was comprised of 100 patients who had experienced ISSNHL within 30 days with no retrocochlear pathology, as demonstrated by a negative MRI scan. 50 patients received 6 intratympanic steroid injections, while the remaining 50 patients received 2 intratympanic injections of PRP at a 1-week interval.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Results:&lt;/b&gt; A total of 39 patients with PRP injection noted an improvement in their hearing of 25 db after 2 weeks and of 30 db after 2 months, with improved speech discrimination of 26% after 2 weeks and of 28% after 2 months. 31 patients with intratympanic steroid injection noted an improvement in their hearing of 18 db after 2 weeks and of 22 db after 2 months, with improved speech discrimination of 21% after 2 weeks and of 24% after 2 months.&lt;/br&gt; &lt;b&gt;&lt;br&gt;Conclusions:&lt;/b&gt; PRP appears safe and efficient for the treatment of ISSNHL, with a low cost and no systemic side effects, as with oral steroids. Therefore, such research should be continued.&lt;/br&gt;

Comparative Study on the Effects of Organic fertilizer (Cow dung), Inorganic Fertilizer (N.P.K) and the Combined Effect of Fertilizers on the Growth Parameters of Strangler Fig (Ficus thonningii)

A comparative study on the effect of organic manure (Cow Dung), inorganic fertilizer (NPK 15-15-15), and their combined effect on the growth of Strangler fig (Ficus thonningii) was carried out at Government Senior Secondary School Dawakin Tofa Local Government Area, Kano State, Nigeria for 28 weeks. The objective of this study was to determine and compare the effect of organic fertilizer (Cow Dung), inorganic fertilizer (N.P.K 15:15:15) and their combined effects on the growth of Ficus thonningii seedlings. The experiment was laid out in a Randomized Complete Block Design (RCBD) with five treatments and a control replicated four times. The treatments consisted of T1= (15g NPK), T2 = (15g CD), T3 = (7.5g NPK: 7.5g CD), T4 = (11.3g NPK + 3.7g CD), T5 = (11.3g CD + 3.7g NPK) and a control (unfertilized) denoted as T6. Various growth parameters such as plant height, number of leaves, plant girth, leaf size and number of branches per plant were measured at 2-week intervals for 7 months. All the data collected were subjected to a two-way analysis of variance (ANOVA) at p&lt;0.05 level of significance using R-software. The results from the experiment showed that most growth characters measured were significantly affected by the application of sole cow dung (15g CD). Thus, based on results obtained in this study, it is suggested to use 15g sole of cow dung for optimum and better growth of Ficus thonningii seedlings in the study area.

Suppression of bone resorption in ovariectomized mice using estrogen-immobilized polyphosphodiesters

Estrogens play a crucial role in bone remodeling. In this study, we synthesized two types of bone-targeted polyphosphodiesters (PPDEs): poly(diethyl sodium phosphate) (PEP•Na) and β-estradiol 17-valerate terminated PEP•Na (E2V-PEP•Na), and determined the inhibitory effect of the terminal estrogen on ovariectomy-induced bone resorption. We first assessed the impact of these polymers on the differentiation of osteoblasts and osteoclasts in vitro. Both PPDEs effectively promoted the differentiation of mouse osteoblastic MC3T3-E1 cells, with E2V-PEP•Na significantly enhancing the mineralization of these cells. Conversely, the density of osteoclasts formed from bone marrow mononuclear cells (BMNCs) significantly decreased when exposed to E2V-PEP•Na. Additionally, the formation of resorption pits on calcium phosphate-coated plates was reduced after treating BMNCs with both PPDEs. We then investigated the role of these polymers in treating osteoporosis using ovariectomized (OVX) mice. PEP•Na or E2V-PEP•Na was separately injected into the tail vein of the mice three times at 2-week intervals, starting 1 day after OVX treatment. Two weeks after the final injection, we observed that E2V-PEP•Na was distributed in bone tissue in a dose-dependent manner. The injection of E2V-PEP•Na significantly reduced bone resorption, and all bone parameters of OVX mice treated with E2V-PEP•Na were superior to those of sham mice. In contrast, PEP•Na did not affect bone mineral metabolism. In conclusion, our study is the first to demonstrate that E2V-PEP•Na can inhibit bone resorption in vivo, offering a promising new polymeric drug for preventing osteoporosis.

Validation, Reliability, and Clinical Significance of the Arabic Version of Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire.

Clinically relevant fatigue in rheumatoid arthritis (RA) patients significantly affects their quality of life. Almost all studies have assessed fatigue in this population using non-specific scales. The present multi-centric study aimed to assess the validity, reliability, and clinical significance of the Arabic version of the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire (BRAF-MDQ). The present cross-sectional multicentric study was conducted at Aswan, Mansoura, Port Said, and Al-Azhar University Hospitals over a 6-month duration. The study included 311 patients with RA diagnosed according to the 2010 criteria of the American College of Rheumatology. The Arabic version of BRAF-MDQ was developed to assess fatigue in these patients. All patients were subjected to careful history taking, thorough clinical assessment, and standard laboratory work-up. The obtained Arabic BRAF-MDQ was tested for construct validity, internal consistency, testretest reproducibility, and criterion validity. Construct validity was evaluated using factor analysis with the Kaiser Meyer Olkin tool of sampling adequacy and Bartlett's sphericity test. Internal consistency of subscales was assessed using Cronbach's alpha. Test-retest reproducibility was assessed after a 1-week interval using the intraclass correlation coefficient. Pearson's correlation coefficient was used to correlate numerical variables. Predictors of fatigue were identified using binary logistic regression analysis. The present study included 311 RA patients. Construct validity assessment showed a high loading of questionnaire items within the proposed construct subscales with a KMO measure of sphericity of 0.927 and Bartlett's test of sphericity p-value < 0.001. Internal consistency assessment showed adequate Cronbach's alpha of Arabic BRAF-MDQ subscales. Total Arabic BRAFMDQ had excellent criterion validity, as indicated by the high correlations with MAFS (r=0.95, p < 0.001) and SF-36 vitality subscale (r=-0.91, p < 0.001). Clinically significant fatigue was identified in 214 patients (68.8%). Multivariate logistic regression analysis revealed age (OR (95% CI): 1.07 (1.02-1.12), p < 0.001), disease duration (OR (95% CI): 1.82 (1.43-2.33), p < 0.001), DAS28CRP (OR (95% CI): 8.62 (4.63-16.02), p < 0.001), and mHAQ (OR (95% CI): 3.85 (1.07-13.9), p = 0 .039) as significant predictors of fatigue development in the studied patients. The Arabic version of the Bristol Rheumatoid Arthritis Fatigue Multi-Dimensional Questionnaire is a valid, consistent, and reliable tool for the assessment of fatigue in Egyptian rheumatoid arthritis patients. Clinically significant fatigue was identified in 214 patients (68.8%). Further, risk factors for fatigue included older age, longer disease duration, and higher disease activity.

Implementation of First-Trimester Screening and Prevention of Preeclampsia: A Stepped Wedge Cluster-Randomized Trial in Asia.

This trial aimed to assess the efficacy, acceptability, and safety of a first-trimester screen-and-prevent strategy for preterm preeclampsia in Asia. Between August 1, 2019, and February 28, 2022, this multicenter stepped wedge cluster randomized trial included maternity/diagnostic units from 10 regions in Asia. The trial started with a period where all recruiting centers provided routine antenatal care without study-related intervention. At regular 6-week intervals, one cluster was randomized to transit from nonintervention phase to intervention phase. In the intervention phase, women underwent first-trimester screening for preterm preeclampsia using a Bayes theorem-based triple-test. High-risk women, with adjusted risk for preterm preeclampsia ≥1 in 100, received low-dose aspirin from <16 weeks until 36 weeks. Overall, 88.04% (42 897 of 48 725) of women agreed to undergo first-trimester screening for preterm preeclampsia. Among those identified as high-risk in the intervention phase, 82.39% (2919 of 3543) received aspirin prophylaxis. There was no significant difference in the incidence of preterm preeclampsia between the intervention and non-intervention phases (adjusted odds ratio [aOR], 1.59 [95% CI, 0.91-2.77]). However, among high-risk women in the intervention phase, aspirin prophylaxis was significantly associated with a 41% reduction in the incidence of preterm preeclampsia (aOR, 0.59 [95% CI, 0.37-0.92]). In addition, it correlated with 54%, 55%, and 64% reduction in the incidence of preeclampsia with delivery at <34 weeks (aOR, 0.46 [95% CI, 0.23-0.93]), spontaneous preterm birth <34 weeks (aOR, 0.45 [95% CI, 0.22-0.92]), and perinatal death (aOR, 0.34 [95% CI, 0.12-0.91]), respectively. There was no significant between-group difference in the incidence of aspirin-related severe adverse events. The implementation of the screen-and-prevent strategy for preterm preeclampsia is not associated with a significant reduction in the incidence of preterm preeclampsia. However, low-dose aspirin effectively reduces the incidence of preterm preeclampsia by 41% among high-risk women. The screen-and-prevent strategy for preterm preeclampsia is highly accepted by a diverse group of women from various ethnic backgrounds beyond the original population where the strategy was developed. These findings underpin the importance of the widespread implementation of the screen-and-prevent strategy for preterm preeclampsia on a global scale. URL: https://www.clinicaltrials.gov; Unique identifier: NCT03941886.

Exploration of the potential of a boosted sterile insect technique to control fruit flies in mango orchards.

An innovative version of the sterile insect technique (SIT) for pest control, called boosted SIT, relies on the use of sterile males coated with a biocide to control a target wild pest population of the same species. The objective of the present study was to assess the relevance of such technology to control the fruit fly Bactrocera dorsalis and fruit losses in mango orchards using. An agent-based simulation model named BOOSTIT was used to explore the reduction of fruit losses thank to sterile male fruit flies control and economic benefits according to different strategies of sterile male release. The simulation considered a landscape of 30.25 ha made up of four mango orchards. The SIT and the boosted SIT reduced fruit losses when releases were made before the mango fruiting period. According to model simulations, releases should be performed at least seven times at 2-week intervals and with a sterile/wild male ratio of at least 10:1. Considering the benefit/cost ratio (BCR), few releases should be done with a late start date. The BCR showed economic gains from the two control methods, the number of saved fruits and BCR being higher for SIT. Our simulations showed that SIT would have better results than the boosted SIT to contribute to an effective control of Bactrocera dorsalis at the scale of a small landscape. We highlight the need for laboratory studies of other types of pathogen to find a suitable one with higher incubation time and lower cost. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Suhu dan Masa Simpan Benih Memengaruhi Viabilitas Benih Mahoni (Swietenia macrophylla King.)

Swietenia macrophylla or big-leaf mahogany is an exotic species from Central and South America. This tree has various benefits, so it’s used as an industrial plantation forest and afforestation in Indonesia. However, seed storage of mahogany is a major problem in cultivation, because it can reduce seed viability. The storability of seeds is influenced by seed and environmental conditions. Therefore, this study aimed to examine the effect of temperature and storage time on the viability of S. macrophylla seeds and to calculate the Seedling Quality Index (SQI). The experiment was carried out using a factorial Randomized Block Design (RBD) with 2 factors. The first factor was consisted of four levels of temperature treatment, namely room temperature (24), 4, 0, and -20°C. The second factor was the storage period treatment which consisted of 4 levels, namely 1 up to 4 weeks, with 1-week intervals. The results showed that the interaction between temperature and storage time affected mahogany leaves, primary and secondary roots, root/shoot ratio, and total wet weight of S. macrophylla seedlings. Mahogany seeds that were stored at room temperature for 1 week resulted in the highest seed viability, with SQI of 0.03-0.04.

Evaluation of a Novel Dermal Cooling System for the Treatment of Benign Pigmented Lesions in Asians.

Our study aimed to evaluate the efficacy of this novel dermal cooling system (DCS) in reducing pigmentation in benign pigmented lesions in Asian patients and its potential side effects. It was a prospective open-label single-center study. Asian patients, with the presence of benign pigmented lesions mainly including lentigines, melasma, nevus spilus, ephelides, café au lait, and seborrheic keratosis were recruited for a novel DCS. The DCS provided localized cooling of the epidermal layer below freezing but was less intense than cryotherapy. Each patient received DCS at Week 0 and repeated at 4-week intervals up to 10 sessions. Global aesthetic improvement scores (GAIS) by blinded physicians and subjects were recorded at 2, 6, and 12 months posttreatment follow-up. Eighty-one patients were recruited with a total of 305 sessions performed and 1716 lesion sites treated. At 2-month posttreatment, 76.5% and 58.6% treatment sites showed obvious to marked improvement respectively and the improvement sustained at 6 and 12 months. Only minor adverse events were reported. Erythema and edema were the most commonly anticipated effects immediately after treatment. The pain was minimal. Postinflammatory hyperpigmentation was only reported in 2.2% (38/1716) treated sites. To our knowledge, this study was the first study to demonstrate that this novel DCS was an effective, safe, and well-tolerated treatment for benign pigmented lesions in Asians.

Effectiveness and safety of primary prophylaxis with G-CSF for patients with Ewing sarcomas: a systematic review for the Clinical Practice Guidelines for the Use of G-CSF 2022 of the Japan Society of Clinical Oncology.

Multidrug chemotherapy for Ewing sarcoma can lead to severe myelosuppression. We proposed two clinical questions (CQ): CQ #1, "Does primary prophylaxis with G-CSF benefit chemotherapy for Ewing sarcoma?" and CQ #2, "Does G-CSF-based intensified chemotherapy improve Ewing sarcoma treatment outcomes?". A comprehensive literature search was conducted in PubMed, Cochrane Library, and Ichushi web databases, including English and Japanese articles published from 1990 to 2019. Two reviewers assessed the extracted papers and analyzed overall survival (OS), febrile neutropenia (FN) incidence, infection-related mortality, quality of life (QOL), and pain. Twenty-five English and five Japanese articles were identified for CQ #1. After screening, a cohort study of vincristine, ifosfamide, doxorubicin, and etoposide chemotherapy with 851 patients was selected. Incidence of FN was 60.8% with G-CSF and 65.8% without; statistical tests were not conducted. Data on OS, infection-related mortality, QOL, or pain was unavailable. Consequently, CQ #1 was redefined as a future research question. As for CQ #2, we found two English and five Japanese papers, of which one high-quality randomized controlled trial on G-CSF use in intensified chemotherapy was included. This trial showed trends toward lower mortality and a significant increase in event-free survival for 2-week interval regimen with the G-CSF primary prophylactic use compared with 3-week interval. This review indicated that G-CSF's efficacy as primary prophylaxis in Ewing sarcoma, except in children, is uncertain despite its common use. This review tentatively endorses intensified chemotherapy with G-CSF primary prophylaxis for Ewing sarcoma.

Obesity Induces Temporally Regulated Alterations in the Extracellular Matrix That Drive Breast Tumor Invasion and Metastasis.

Obesity is associated with increased incidence and metastasis of triple-negative breast cancer, an aggressive breast cancer subtype. The extracellular matrix (ECM) is a major component of the tumor microenvironment that drives metastasis. To characterize the temporal effects of age and high-fat diet (HFD)-driven weight gain on the ECM, we injected allograft tumor cells at 4-week intervals into mammary fat pads of mice fed a control or HFD, assessing tumor growth and metastasis and evaluating the ECM composition of the mammary fat pads, lungs, and livers. Tumor growth was increased in obese mice after 12 weeks on HFD. Liver metastasis increased in obese mice only at 4 weeks, and elevated body weight correlated with increased metastasis to the lungs but not the liver. Whole decellularized ECM coupled with proteomics indicated that early stages of obesity were sufficient to induce changes in the ECM composition. Obesity led to an increased abundance of the proinvasive ECM proteins collagen IV and collagen VI in the mammary glands and enhanced the invasive capacity of cancer cells. Cells of stromal vascular fraction and adipose stem and progenitor cells were primarily responsible for secreting collagen IV and collagen VI, not adipocytes. Longer exposure to HFD increased the invasive potential of ECM isolated from the lungs and liver, with significant changes in ECM composition found in the liver with short-term HFD exposure. Together, these data suggest that changes in the breast, lungs, and liver ECM underlie some of the effects of obesity on triple-negative breast cancer incidence and metastasis. Significance: Organ-specific extracellular matrix changes in the primary tumor and metastatic microenvironment are mechanisms by which obesity contributes to breast cancer progression.

Efficacy and Safety of 577-nm Yellow Laser in the Treatment of Pigmented Epidermal Lesions.

Freckles and lentigines are common pigmented problems which not only cause substantial cosmetic morbidity but also create psychosocial concern. The available modalities for the treatment of pigmented lesions are often unsatisfactory for patients, require a long treatment period, and often cause skin irritation. With the advent of lasers, safe and effective treatment options for epidermal pigmentation have become more varied for different Fitzpatrick skin types. We aimed to evaluate the efficacy and safety of 577-nm yellow laser in the treatment of pigmented epidermal lesions. This study was carried out on 50 patients presented with pigmented epidermal lesions (25 presented with freckles and 25 presented with lentigines). Each patient received four treatment sessions with a 577-nm diode laser at 2-week intervals. There was significant improvement in freckles and lentigines, as 23 out of 50 patients showed marked improvement, 11 patients showed moderate improvement, 10 patients showed mild improvement, and only six patients had no changes. Moreover, 23 patients were very satisfied, 18 patients were satisfied, and nine patients were not satisfied. As regards the safety of the 577-nm yellow laser, there was no significant adverse effect among patients except pain, erythema, and hyperpigmentation, which resolved within one month after treatment. This study showed that the 577-nm yellow laser is an effective, safe, and well-tolerated device in the treatment of freckles and lentigines.

Using an Uptake Enhancer to Mitigate Nitrogen Leaching While Enhancing Uptake Efficiency

Nitrogen (N) has the most crucial influence on raising agricultural productivity of all other plant nutrients given to crops. However, 50% of the N given to crops is dissipated to the environment globally, resulting in environmental concerns due to leaching. Current research shows that intensive agricultural production systems, which are still used in a large proportion around the world, are prone to N loss. This study aimed to investigate the effect of uptake enhancer applications on N movement in the soil profile based on 10 cm depth intervals, as well as its effects on N uptake and vegetative growth of oats at 4-week intervals over a 16-week period, using sandy soil as a growing medium. Oats were cultivated in a glasshouse setting in polyvinyl chloride (PVC) columns of 60 cm in height. Six treatments were employed at the 3rd leaf growth stage, and each was replicated four times. The experiment had a constructive and a destructive part, which was employed to monitor crop N uptake at four growth stages. Analyses of soil and plant samples were carried out in all the growth stages. The treatments containing the uptake enhancer prevented N from leaching, particularly at the top 20 cm soil depth, with impressive reductions of 194% at 0–10 cm depth and 186% at 10–20 cm depth, during the first 4 weeks after planting. The uptake enhancer also promoted early vegetative growth and crop performance with 15%. In conclusion, the study revealed that employing the uptake enhancer can improve the efficacy of N fertilizer, thereby reducing the application rate of the fertilizer in agroecosystems.

Effects of combining a high-intensity interval training programme with a standard programme on mobility and function in lower limb amputees.

High-energy expenditure during walking is one of the most important limiting factors for lower limb amputees. Although several physical training methods have been proposed to reduce energy expenditure, little is known about the effects of high-intensity interval training in lower limb amputees. This study aimed to test the effects of a 6-week high-intensity interval training protocol in subjects with lower limb amputation on walking distance, physiological cost of walking, and functional mobility. A quasi-experimental pre and post-study included 13 subjects with lower limb amputation. They performed 12 sessions of a high-intensity interval training protocol with a frequency of 2 days/week for 6 weeks. Walking distance, physiological cost of walking, and functional mobility before and after the training protocol were assessed. Walking distance increased from 204.48 to 229.09 m ( P = 0.003), physiological cost of walking decreased from 0.66 to 0.31 beats/m ( P = 0.001), and functional mobility improved from 30.38 to 33.61 points ( P = 0.001). High-intensity interval training improved walking distance, physiological cost of walking, and functional mobility in subjects with lower limb amputation.

Short-Term Real-World Outcomes of Intensive Aflibercept Injection for Refractory Neovascular Age-Related Macular Degeneration.

Background: The aim of this study is to report short-term outcomes after the shortening of the treatment interval to 4 weeks with a treat-and-extend (TAE) regimen (Si4w) of aflibercept in patients with refractory neovascular age-related macular degeneration (nAMD). Methods: This retrospective study included 34 patients given aflibercept with a TAE regimen of a minimum of a 4-week interval when they had a limited response to bimonthly aflibercept. The best-corrected visual acuity (BCVA) and central macular thickness (CMT) were compared before and after Si4w. The resolution of subretinal and intraretinal fluid before and after Si4w was also examined. The risk factors associated with persistent fluid were analyzed. Results: The average treatment duration until initiation of Si4w was 57.82 ± 28.59 months, with an average of 23.64 ± 12.40 injections administered. The BCVA was not significantly improved after Si4w. The CMT decreased significantly from 427.91 ± 125.74 μm to 336.38 ± 121.67 μm at the third visit (p < 0.001). Eighteen eyes (52.9%) showed complete resolution, and twenty-three eyes (67.6%) experienced complete resolution at least once during the three visits. The duration of fluid before Si4w was significantly associated with complete resolution (p = 0.011). Conclusions: Si4w of aflibercept showed satisfactory anatomical outcomes with complete resolution of fluid in patients with a limited response to bimonthly aflibercept injections, and should be considered as a useful treatment option.