Treatment Options Research Articles

Treatment for paraganglioma with stereotactic radiotherapy

BACKGROUND Paragangliomas (PG) are rare neoplasms of neuroendocrine origin that tend to be highly vascularized, slow-growing, and usually sporadic. To date, common treatment options are surgical resection (SR), with or without radiation therapy (RT), and a watch-and-wait approach. AIM To evaluate the local control and effectiveness of exclusive fractionated stereotactic RT (FSRT) treatment in unresectable PG (uPG). METHODS We retrospectively evaluated patients with uPG (medically inoperable or refused SR) treated with FSRT with a Cyberknife System (Accuray Incorporated, Sunnyvale, California). Toxicity and initial efficacy were evaluated. RESULTS From May 2009 to January 2023, 6 patients with a median age of 68 (range 20-84) were treated with FSRT. The median delivered dose was 21 Gy (range 20-30 Gy) at a median isodose line of 75.5% (range 70%-76%) in 4 fractions (range 3-5 fractions). The median volume was 13.6 mL (range 12.4-65.24 mL). The median cumulative biological effective dose and equivalent dose in 2-Gy fractions were 70 Gy and 37.10 Gy respectively. Site of origin involved were the timpa-nojugular glomus (4/6), temporal bone, and cervical spine. In 1 of the 6 patients, the follow-up was insufficient; 5 of 6 patients showed a 5-year overall survival and 5-year progression-free survival of 100%. We observed negligible toxicities during and after RT. The majority of patients showed stable symptoms during follow-up. Only 1 patient developed spine metastases. CONCLUSION Our preliminary results on this small cohort of patients suggest that FSRT could be an effective and safe alternative to SR.

Advanced nanomedicines and immunotherapeutics to treat respiratory diseases especially COVID-19 induced thrombosis

Immunotherapy and associated immune regulation strategies gained huge attraction in order to be utilized for treatment and prevention of respiratory diseases. Engineering specifically nanomedicines can be used to regulate host immunity in lungs in the case of respiratory diseases including coronavirus disease 2019 (COVID-19) infection. COVID-19 causes pulmonary embolisms, thus new therapeutic options are required to target thrombosis, as conventional treatment options are either not effective due to the complexity of the immune-thrombosis pathophysiology. In this review, we discuss regulation of immune response in respiratory diseases especially COVID-19. We further discuss thrombosis and provide an overview of some antithrombotic nanoparticles, which can be used to develop nanomedicine against thrombo-inflammation induced by COVID-19 and other respiratory infectious diseases. We also elaborate the importance of immunomodulatory nanomedicines that can block pro-inflammatory signalling pathways, and thus can be recommended to treat respiratory infectious diseases.

Eruptive xanthomas in a patient with severe hypertriglyceridemia: A case report

BACKGROUND Xanthomatosis, a metabolic disorder causing yellow growths (xanthomas), poses challenges in lipid metabolism. This case study introduces the first documented instance within China's Yi population, emphasizing the need to explore dietary habits and treatment strategies tailored to this specific community. CASE SUMMARY Xanthomatosis is a metabolic disorder where lipid metabolism goes awry, resulting in the development of yellowish growths called xanthomas. A male patient, 47 years of age, from China's Yi population, who is obese, visited our dermatology clinic complaining of widespread, non-painful rashes that have been present for two weeks. The patient works as a chef and has a diet that frequently includes oily and greasy foods. This case represents the initial documentation of xanthomatosis within the Yi population in China, offering a theoretical foundation for understanding dietary patterns and treatment options specific to the Yi community. CONCLUSION The first report of xanthomatosis in the Yi population in China lays a theoretical foundation for understanding Yi dietary patterns and treatment.

Migration of varicocele coil leading to ureteral obstruction and hydronephrosis: A case report

BACKGROUND Varicocele embolization, a minimally invasive treatment for symptomatic varicoceles, carries a rare risk of complications like ureteral obstruction and hydronephrosis. This case report documents such a case to raise awareness of these potential complications and showcase minimally invasive surgical management as a successful solution. CASE SUMMARY A 35-year-old male presented with flank pain and hematuria following varicocele embolization. Imaging confirmed left ureteral obstruction and hydronephrosis. Laparoscopic ureterolysis successfully removed the embolization coil and repaired the ureter, resolving the patient's symptoms. Follow-up at six months and two years showed sustained improvement. CONCLUSION Minimally invasive surgery offers an effective treatment option for rare complications like ureteral obstruction arising from varicocele embolization.

The Effect of a Pilot Brief Educational Intervention on Preferences Regarding Treatments for Opioid Use Disorder

PurposeNegative perceptions around medications for opioid use disorder (MOUD) amongst the public could deter patients with opioid use disorder (OUD) from engaging with MOUD. Thus, we evaluated whether a brief intervention could improve preferences for MOUD in people who may or may not use opioids. MethodsWe employed a pre-post design to assess the effect of a brief educational intervention on preferences for methadone, buprenorphine, naltrexone, and non-medication treatment in an online sample of US adults stratified by race, who may or may not use opioids. Respondents ranked their preferences in OUD treatment before and after watching four one-minute educational videos about treatment options. Changes in treatment preferences were analyzed using Bhapkar’s test and post hoc McNemar’s tests. A binary logistic generalized estimating equation (GEE) assessed factors associated with preference between treatments. ResultsThe sample had 530 responses. 194 identified as White, 173 Black, 163 Latinx. Treatment preferences changed significantly towards MOUD (p<.001). This effect was driven by changes toward buprenorphine (OR=2.38; p<.001) and away from non-medication treatment (OR=0.20; p<.001). There was no significant difference in effect by race/ethnicity. People with lower opioid familiarity were significantly more likely to change their preferences towards MOUD following the intervention. ConclusionRespondent preferences for MOUD increased following the intervention suggesting that brief educational interventions can change treatment preferences towards MOUD. These findings offer insights into perceptions of OUD treatment in a racially stratified sample and serve as a foundation for future educational materials that target MOUD preferences in the general public.

Hederagenin Improves Adriamycin-induced Nephropathy by Inhibiting the JAK/STAT Signaling Pathway

ABSTRACT Background: Glomerulonephritis, a common kidney disease and major cause of end-stage renal disease, lacks effective treatment options. Hederagenin (HDG) exerts potent anti-inflammatory and protective effects on the kidneys and exhibits promise for the treatment of glomerulonephritis. This study aimed to investigate the therapeutic effects and mechanism of action of hederagenin in the context of adriamycin-induced nephropathy (ADN). Methods: C57BL/6 mice were randomly divided into 5 groups that included the control, model, low-dose HDG (20 mg/kg), high-dose HDG (40 mg/kg), and positive control (10 mg/kg irbesartan) groups. ADN was established in mice by administering a single injection of 10 mg/kg adriamycin. Renal pathology and fibrosis were assessed using haematoxylin and eosin (H &amp; E) and Masson’s trichrome staining, whereas in vitro studies were conducted using cultured mouse podocytes (MPC5). Immunofluorescence staining and western blotting were performed to detect inflammation and the protein levels of signaling pathways. Results: The results revealed that HDG significantly improved adriamycin-induced abnormal serum creatinine, albumin, and urea nitrogen levels. HDG treatment reduced glomerular injury and fibrosis, particularly at high doses. Additionally, HDG effectively reduced adriamycin-induced activation of Janus kinase-signal transducer and activator of transcription (JAK/STAT) signaling and renal fibrosis while suppressing CD4+/CD8+ cell ratios in the kidneys and enhancing the immune response. Interestingly, when the JAK/STAT signaling pathway was activated by an agonist, the ameliorative effects of HDG on ADN were inhibited, thus suggesting that JAK/STAT signaling is a key target of HDG. Conclusion: HDG may represent a promising treatment option for glomerulonephritis by inhibiting JAK/STAT-mediated immune-inflammatory responses.

Investigating the Influence of Gut Microbiota-related Metabolites in Gastrointestinal Cancer.

Gastrointestinal (GI) cancer is a major health concern due to its prevalence, impact on well-being, high mortality rate, economic burden, and potential for prevention and early detection. GI cancer research has made remarkable strides in understanding biology, risk factors, and treatment options. An emerging area of research is the gut microbiome's role in GI cancer development and treatment response. The gut microbiome, vital for digestion, metabolism, and immune function, is increasingly linked to GI cancers. Dysbiosis and alterations in gut microbe composition may contribute to cancer development. Scientists study how specific bacteria or microbial metabolites influence cancer progression and treatment response. Modulating the gut microbiota shows promise in enhancing treatment efficacy and preventing GI cancers. Gut microbiota dysbiosis can impact GI cancer through inflammation, metabolite production, genotoxicity, and immune modulation. Microbes produce metabolites like short-chain fatty acids, bile acids, and secondary metabolites. These affect host cells, influencing processes like cell proliferation, apoptosis, DNA damage, and immune regulation, all implicated in cancer development. This review explores the latest research on gut microbiota metabolites and their molecular mechanisms in GI cancers. The hope is that this attempt will help in conducting other relevant research to unravel the precise mechanism involved, identify microbial signatures associated with GI cancer, and develop targets.

Low subcutaneous adipose tissue and myosteatosis are prognostic factors after allogeneic hematopoietic stem cell transplantation

ObjectiveAllogeneic hematopoietic stem cell transplantation (allo-HSCT) represents the only curative treatment option for several hematological neoplasms. This study aimed to assess the parameters of body composition as predictors of posttransplant overall survival (OS) and adverse events in patients with leukemia, myelodysplastic syndromes (MDS), and myeloproliferative neoplasms (MPN). MethodsThis was a retrospective study of 122 adult patients who underwent their first allo-HSCT. The CT-based semi-automated measurement of subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT), visceral-to-subcutaneous fat ratio (VSR), sarcopenia in terms of skeletal muscle index (SMI), and myosteatosis based on the skeletal muscle radiation attenuation (SM-RA) was performed. Cox regression analysis was used to assess the association of body composition parameters with OS. ResultsIn the univariate analysis, low SAT and myosteatosis were associated with lower OS (hazard ratio [HR] 2.02, 95% confidence interval [CI] 1.16–3.51, p = 0.01) and (HR 2.50, 95% CI 1.48 – 4.25, p=< 0.001), respectively. This association remained significant after adjusting for relevant covariates, with HR 2.32, 95% CI 1.23 – 4.38, p=0.01 and HR 2.86, 95% CI 1.51 – 5.43, p=< 0.001, respectively. On the contrary, VAT, VSR, sarcopenia, and sarcopenic obesity were not statistically significant in OS. Severe post-transplant adverse events were more common in the low SAT group (odds ratio [OR] 3.12, 95% CI 1.32– 7.40, p=0.01) and OR 3.17, 95% CI 1.31 – 7.70, p=< 0.01 in the age- and sex-adjusted analysis. ConclusionLow SAT and myosteatosis may contribute to an increased risk of mortality, while low SAT appears to increase the risk of severe post-transplant adverse events.

Rapidly Growing Congenital Disseminated Pyogenic Granuloma in the Scalp Treated with Staged Embolization and Excision: A Case Report

Pyogenic granulomas are common, acquired vascular lesions that most often arise spontaneously or in sites of previous trauma. However, there are reports of a few cases that describe a rare condition, congenital disseminated pyogenic granuloma (CDPG), in which an infant either is born with or shortly after birth develops multiple pyogenic granulomas. A hallmark of CDPG is negative staining for glucose transporter 1 (GLUT-1) on immunohistochemistry, which helps distinguish it from the more common multifocal infantile hemangiomas. Because few case reports have described CDPG, much is unknown about its characteristics, clinical course, and most effective treatment options. Here, we present a case of an infant with a unique presentation of CDPG with lesions that are atypically large and growing at a rapid pace. We also describe a novel approach to treating large pyogenic granulomas in CDPG via staged glue embolization and surgical excision.

Comparing the efficacy of a novel mucoadhesive patch containing Nigella sativa 10% with triamcinolone 0.1% in patients with erosive-atrophic oral lichen planus: A pilot study.

This study evaluates the efficacy of a novel mucoadhesive patch containing Nigella sativa 10% extract compared to triamcinolone 0.1% in alleviating symptoms and reducing lesion severity in patients with erosive-atrophic oral lichen planus. A pilot study comprising two groups, each with 10 patients, was conducted. The intervention group received mucoadhesive patches containing N. sativa 10% extract, while the control group received triamcinolone acetonide 0.1% patches. Pain and burning intensity, measured through visual analog scale, and lesion severity based on the Thongprasom scale were assessed weekly for 4 weeks. Descriptive records were kept for side effects and patient satisfaction. Pain and burning intensity decreased in both groups throughout the sessions, with the N. sativa group showing a greater reduction than the triamcinolone group. The reduction in burning intensity within each group was significant (p < .001), and there was a significant difference between groups only in the second session (p = .045). The overall difference between groups was not significant (p > .05). Lesion severity also decreased significantly in both groups (p < .001), with a significant difference between groups observed in the third session (p = .043) and overall throughout the study (p = .006). The use of N. sativa extract in mucoadhesive patches was as effective as corticosteroids in reducing pain, burning, and lesion severity in patients with oral lichen planus, with N. sativa showing superior results in some sessions. Notably, no significant complications were observed with N. sativa use, making it a promising treatment option for lichen planus.

Review article: Patients who leave before care is completed: What does the legal duty to warn mean for emergency department clinicians?

Patients leave ED for a variety of reasons and at all stages of care. In Australian law, clinicians and health services owe a duty of care to people presenting to the ED for care, even if they have not yet entered a treatment space. There is also a positive duty to warn patients of material risks associated with their condition, proposed treatment(s), reasonable alternative treatment options and the likely effect of their healthcare decisions, including refusing treatment. This extends to a decision to leave the ED before care is completed. The form of that warning may vary based on what is known about the patient's condition and the associated risks at the time. Specific documentation of warnings given is essential.

Targeted treatment options for paediatric B-cell precursor acute lymphoblastic leukaemia patients with constitutional or somatic chromosome 21 alterations

BackgroundChromosome 21 is affected in ~60% of paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) patients and includes somatic and constitutional gains, intrachromosomal amplification of chromosome 21 (iAMP21), and the translocation t(12;21) resulting in the ETV6::RUNX1 gene fusion. MethodsSince these numeric and structural chromosome 21 alterations are not targetable, we studied the type and frequency of yet-proven targetable events co-occurring with chromosome 21 alterations. ResultsAmong 307 primary paediatric BCP-ALL cases, JAK/STAT pathway lesions were most frequent in patients with constitutional gain of chromosome 21 (Down syndrome ALL; 35/71, 49%) and iAMP21 (9/22, 41%). RAS pathway lesions were most frequent in high hyperdiploidy (62/108, 57%) and FLT3 lesions were most frequent in iAMP21 (7/22, 32%). Virtually all cases expressed CD19 and CD22 at the cell surface. Positivity for CD20 surface expression ranged from 67% in iAMP21 (8/12) to 20% in ETV6::RUNX1 (26/129). ConclusionActivated JAK/STAT, RAS or FLT3 signalling, and CD marker surface expression may provide targetable treatment options for the majority of chromosome 21-altered BCP-ALL cases.

State-of-the-Art Management of Colorectal Cancer: Treatment Advances and Innovation.

Colorectal cancer (CRC) remains a significant global health challenge, ranking among the leading causes of cancer-related morbidity and mortality worldwide. Recent advancements in molecular characterization have revolutionized our understanding of the heterogeneity within colorectal tumors, particularly in the context of tumor sidedness. Tumor sidedness, referring to the location of the primary tumor in either the right or left colon, has emerged as a critical factor influencing prognosis and treatment responses in metastatic CRC. Molecular underpinnings of CRC, the impact of tumor sidedness, and how this knowledge guides therapeutic decisions in the era of precision medicine have led to improved outcomes and better quality of life in patients. The emergence of circulating tumor DNA as a prognostic and predictive tool in CRC heralds promising advancements in the diagnosis and monitoring of the disease. This innovation facilitates better patient selection for exploration of additional treatment options. As the field progresses, with investigational agents demonstrating potential as future treatments for refractory metastatic CRC, new avenues for enhancing outcomes in this challenging disease are emerging.

Blood Purification for the Treatment of Chronic Kidney Disease-associated Pruritus

ABSTRACT Chronic kidney diseases-associated pruritus (CKD-aP) is a term that indicates the itching associated to end stage kidney disease without any apparent cause. This symptom leads to decreased quality of life and increased risk of long-term morbidities and mortality. The pathogenesis of uremic pruritus is still unknown, however, different theories have merged: uremic toxins deposition, immune system dysregulation, peripheral neuropathy, and opioid imbalance. While in the last decade, research focused prevalently on pharmaceutical treatment of CKD-aP, extracorporeal therapies have also evolved providing an alternative but efficient treatment option. In this review, we assess the role of different extracorporeal methods on the treatment of CKD-aP.

Oral azacitidine compared with standard therapy in patients with relapsed or refractory follicular helper T-cell lymphoma (ORACLE): an open-label randomised, phase 3 study

Follicular helper T-cell lymphomas (TFHL) harbour frequent alterations in genes that regulate DNA methylation. Preliminary reports suggest that treatment with 5-azacitidine has clinical activity in patients with relapsed or refractory TFHL. We aimed to compare the oral form of azacitidine with investigator's choice standard therapy (ICT; ie, gemcitabine, bendamustine, or romidepsin) in patients with relapsed or refractory TFHL. Patients older than 18 years with relapsed or refractory TFHL (angioimmunoblastic T-cell lymphoma, follicular lymphoma, or nodal T-cell lymphoma with phenotype, ie, positive with two or more markers among CD10, BCL6, CXCL13, PD1, or ICOS) based on the 2017 WHO classification of haematological neoplasms, with an Eastern Cooperative Oncology Group performance status score of 0-3, were recruited in university hospitals from five European countries and from Japan. Patients were randomly assigned 1:1 to treatment with either azacitidine given at a dose of 300 mg once a day (200 mg in Japanese patients) for 14 days in a 28-day cycle or gemcitabine, bendamustine, or romidepsin according to the investigator's choice. Random assignment was stratified by the number of previous lines of therapy and by the presence of previous or concomitant myeloid malignancy. The primary endpoint was investigator-assessed progression-free survival, presented in the intention-to-treat population. This Article is the final analysis of this trial, registered at ClinicalTrials.gov (Europe NCT03593018 and Japan NCT03703375). 86 patients (median age 69 years [IQR 62-76], 50 patients were male, 36 were female) were enrolled between Nov 9, 2018, to Feb 22, 2021; 42 in the azacitidine group and 44 in the ICT group. With a median follow-up of 27·4 months (IQR 20·2-32·9), the median progression-free survival was 5·6 months (95% CI 2·7 -8·1) in the azacitidine group versus 2·8 months (1·9-4·8) in the ICT group (hazard ratio of 0·63 (95% CI 0·38-1·07); 1-sided p=0·042). Grade 3-4 adverse events were reported in 32 (76%) of 42 patients in the azacitidine group versus 42 (98%) of 43 patients in the ICT group. The most adverse grade 3 or worse adverse events were haematological (28 [67%] of 42 patients vs 40 [93%] of 43 patients), infection (8 [19%] and 14 [33%]), and gastrointestinal (5 [12%] vs 1 [2%] for azacitidine and ICT, respectively). There were two treatment-related deaths in the azacitidine group (one endocarditis and one candidiasis) and three in the ICT group (one heart failure, one COVID-19, and one cause unknown). Although the pre-specified primary outcome of the trial was not met, the favourable safety profile suggests that azacitidine could add to the treatment options in these difficult to treat diseases especially in combination with other drugs. Trials with combination are in preparation in a platform trial. Bristol-Myers Squibb. For the French translation of the abstract see Supplementary Materials section.

The Italian law 219/2017: informed consent and advance directives. When the patient-doctor communication time is law, but it is forgotten

The Italian law 217/2019 on "Informed consent and advance directives" is an important step forward in the redefinition of patient-doctor relationships. The law points out the principles of the decisional autonomy and freedom of the patient to choose the treatment options. However, it is underestimated and largely unapplied by the Italian cardiologists. The main elements of patient-doctor communication are present in the law. The most important is the time devoted to the patient-doctor relationship, necessary to ease the disease awareness. This time is clearly emphasized in the law, but the healthcare institutions did not arrange for the appropriate organizational procedures. Through the advance directives (ADs) the patients may express their own wishes about healthcare treatments, as well as their consent or refusal regarding the diagnostic or therapeutical doctors' suggestions, allowing their respect in case they become incompetent. This right is supported by the patients' designation of a healthcare proxy, who can interact for them with the healthcare team. However, after 6 years since the law enactment, only 0.4% of the Italian citizens signed ADs, due to insufficient information and organization by the healthcare authorities. In the Law, the advance care planning is closely related to ADs. In this process, the adults can understand and share their personal values, life goals and preferences, in order to define the potential future medical care and to discuss all the issues with family and physicians. These processes can be integrated in a broader shared decision-making, a strong tool of the patient-doctor alliance.

Effects of a ketogenic diet on motor function and motor unit number estimation in aged C57BL/6 mice

ObjectivePathological, age-related loss of muscle function, commonly referred to as sarcopenia, contributes to loss of mobility, impaired independence, as well as increased risk of adverse health events. Sarcopenia has been attributed to changes in both neural and muscular integrity during aging. Current treatment options are primarily limited to exercise and dietary protein fortification, but the therapeutic impact of these approaches are often inadequate. Prior work has suggested that a ketogenic diet (KD) might improve healthspan and lifespan in aging mice. Thus, we sought to investigate the effects of a KD on neuromuscular indices of sarcopenia in aged C57BL/6 mice. DesignA randomized, controlled pre-clinical experiment consisting of longitudinal assessments performed starting at 22-months of age (baseline) as well as 2, 6 and 10 weeks after the start of a KD vs. regular chow intervention. SettingPreclinical laboratory study. Sample sizeThirty-six 22-month-old mice were randomized into 2 dietary groups: KD [n = 22 (13 female and 9 male)], and regular chow [n = 15 (7 female and 8 male)]. MeasurementsMeasures included body mass, hindlimb and all limb grip strength, rotarod for motor performance, plantarflexion muscle contractility, motor unit number estimations (MUNE), and repetitive nerve stimulation (RNS) as an index of neuromuscular junction transmission efficacy recorded from the gastrocnemius muscle. At end point, muscle wet weight and blood samples were collected to assess blood beta-hydroxybutyrate levels. Statistical analysisPrimary analyses were two-way mixed effects ANOVA (diet and time × diet) to determine the effect of a KD on indices of motor function (grip, rotarod) and indices of motor unit (MUNE) and muscle (contractility) function. ResultsBeta-hydroxybutyrate (BHB) was significantly higher at 10 weeks in mice on a KD vs control group (0.83 ± 0.44 mmol/l versus 0.42 ± 0.21 mmol/l, η2 = 0.265, unpaired t-test, p = 0.0060). Mice on the KD intervention demonstrated significantly increased hindlimb grip strength (diet, p = 0.0001; time × diet, p = 0.0030), all limb grip strength (diet, p = 0.0005; time × diet, p = 0.0523), and rotarod latency to fall (diet, p = 0.0126; time × diet, p = 0.0021). Mice treated with the KD intervention also demonstrated increased MUNE (diet, p = 0.0465; time × diet, p = 0.0064), but no difference in muscle contractility (diet, p = 0.5248; time × diet, p = 0.5836) or RNS (diet, p = 0.3562; time × diet, p = 0.9871). ConclusionKD intervention improved neuromuscular and motor function in aged mice. This pre-clinical work suggests that further research is needed to assess the efficacy and physiological effects of a KD on indices of sarcopenia.

Evaluating Pollination and Weed Control Strategies under Mesotunnel Systems for Organic Muskmelon Production in Iowa

Bacterial wilt of cucurbits, caused by Erwinia tracheiphila, is spread by spotted (Diabrotica undeimpunctata howardi) and striped (Acalymma vittatum) cucumber beetles and results in major losses for US cucurbit (Cucurbitaceae spp.) growers. Organic growers of muskmelon (Cucumis melo) lack reliable control measures against bacterial wilt. During previous field trials in Iowa, USA, a system called mesotunnels, which are 3.5-ft-tall barriers covered with a nylon mesh insect netting, resulted in a higher marketable yield of organic ‘Athena’ muskmelon than low tunnels or noncovered plots. However, satisfactory pollination and weed control are challenging in mesotunnels because the netting covers the crop for most or all of the growing season, and economic feasibility of these systems has not been determined. Consequently, two field trials conducted in Iowa from 2020 to 2022 evaluated strategies to ensure pollination under mesotunnels in commercial-scale plots, assess effectiveness of teff (Eragrostis tef) as a living mulch for weed control in mesotunnel systems, and compare the profitability of the treatment options for organic ‘Athena’ muskmelon. The treatments used during the pollination trial were as follows: full season, in which mesotunnels remained sealed all season and bumble bees (Bombus impatiens) were added at the start of bloom for pollination; open ends, wherein both ends of the tunnels were opened at the start of bloom then reclosed 2 weeks later; and on-off-on, in which nets were removed at the start of bloom and then reinstalled 2 weeks later. The full-season treatment had significantly higher marketable yield than the other treatments in two of three trial years. Plants with the full season and open ends treatments had a bacterial wilt incidence &lt;2.5% across all three years and similar numbers of cucumber beetles, whereas plants with the on-off-on treatment had an average bacterial wilt incidence of 11.0% and significantly more cucumber beetles. The open ends treatment had fewer bee visits to ‘Athena’ muskmelon flowers than the other treatments. In the 2-year (2021–22) weed management trial, treatments applied to the furrow between plastic-mulched rows were as follows: landscape fabric; teff seeded at 4 lb/acre and mowed 3 weeks after seeding; teff seeded at 4 lb/acre and not mowed; a control with bare ground where weeds were mowed 3 weeks after transplanting; and a bare ground control with no mowing. The landscape fabric and mowed teff treatments had statistically similar marketable yield, and mowing appeared to minimize yield losses compared with nonmowed treatments. The landscape fabric had no weeds, followed by mowed teff, mowed bare ground, and nonmowed teff. Nonmowed bare ground had the highest weed biomass. The partial budget and cost-efficiency ratio analysis indicated that the full-season treatment was the most cost-efficient pollination option for mesotunnel systems. An economic analysis of the weed management strategies showed that using teff as a living mulch in the furrows between organic ‘Athena’ muskmelon rows, coupled with timely mowing to suppress its growth, can generate revenue comparable to that of landscape fabric. Our findings suggest that organic ‘Athena’ muskmelon growers in Iowa may gain the greatest yield and soil quality benefits when mesotunnels are kept closed for the entire season, bumble bees are used for pollination, and teff (mowed 3 weeks after seeding) is used to control weeds in the furrows. Further trials integrating these pollination and weed management strategies would help validate a comprehensive approach to organic ‘Athena’ muskmelon production under mesotunnels.

Multicomponent Intervention Is an Effective Treatment Option for Overactive Bladder in Women.

According to this study: A randomized clinical trial showed that a multicomponent intervention with cognitive components improved health-related quality of life in women with moderate-to-severe overactive bladder.

Molecular docking and dynamics simulation reveal withanolides as potent antivirals against dengue virus

The prevalence of dengue remains a significant global threat to public health with millions of infections reported annually due to the lack of effective treatment options. Natural resources such as plants contain phytochemicals with desirable therapeutic effects. For instance, the Indian ginseng, Withania somnifera L. (Solanaceae), contains steroidal lactones, saponins, glycosides, and alkaloids which possessed antiviral activities against various viruses. In this study, docking analysis of seven compounds and phytochemicals were performed against the structural and non-structural (NS) proteins of all four dengue virus (DENV) serotypes as well as host cell receptors such as DC-SIGN and CLEC5A. Withanolide A (L5) was selected as the best inhibitor with high binding affinities towards ten targets consisting of DENV structural and NS proteins as well as the CLEC5A receptor. L5 also showed a fair stability with DENV1, DENV2, and DENV3 over a time span of 100 ns via molecular dynamics simulation. L5 demonstrated good drug-likeness properties, a moderate bioavailability score of 0.55, and is predicted to have high gastrointestinal absorptivity. The data from this in silico study revealed the potential of withanolide A to be further developed as an antiviral against dengue. This is the first study to report the in silico analyses of phytochemicals derived from W. somnifera L. (Solanaceae) against the viral proteins of DENV1 to 4 and their respective host cell receptors.