Effect Profile Research Articles

Textural profile characteristic of the curd mass from camel milk for gero diet

There are not so many fermented milk products recommended for use in gerodiet. Among them, for the first time, the textural characteristics of curd mass made from camel milk with the addition of flaxseed flour were investigated. As a result of the study, it was found that camel milk curd differs in hardness, adhesion and distribution compared to cow milk curd. In terms of adhesion, the camel milk curd was 44.52% higher than the cow milk curd and 85% lower than the cow and camel milk curd. The adhesion of the curd mass from cow's milk was the least important among the curd mass. It was noted that the time taken to dispense the camel curd was 50% less than the time taken to dispense the cow's milk curd. However, all samples of curd mass did not differ significantly in hardness. As a result of the study, it can be concluded that camel milk curd mass in terms of chewing, distribution and firmness can have an effective texture profile compared to other samples.

Anti-Inflammatory Effects of Thymoquinone in Atherosclerosis: A Mini Review

Atherosclerosis poses serious health problems and increases the risk of various cardiovascular diseases, including myocardial infarction, heart failure, ischemic stroke, and peripheral arterial disease. Atherosclerosis patients require long-term medications to prevent complications, some of which are costly and may result in unwanted adverse reactions. Natural products have emerged as potential sources of bioactive compounds that provide health benefits in cardiovascular diseases. Increased inflammation and vascular remodeling have been associated with atherosclerosis pathogenesis. The molecules involved in signaling pathways are considered valuable targets for new treatment approaches. Therefore, this review aimed to summarize the available evidence of the anti-inflammatory effects of thymoquinone, the major active compound isolated from Nigella sativa L., via inflammatory signaling pathways in atherosclerosis. Specifically, nuclear factor-κB and mitogen-activated protein kinase signaling pathways were considered. Furthermore, the potential toxic effects elicited by thymoquinone were addressed. These findings suggest a potential role of thymoquinone in managing atherosclerosis, and further studies are required to ascertain its effectiveness and safety profile.

Comparing the affective and social effects of positive reappraisal and minimising reappraisal

ABSTRACT Negative interpersonal events, such as close relationship conflicts, can threaten one’s affective and social well-being. To improve affect and to maintain valuable relationships, individuals could select different reappraisal tactics. One could use positive reappraisal to find potential benefits of the event (e.g. “This conflict helps our relationship grow.”), or use minimising reappraisal to decrease the perceived impact of event (e.g. “This is no big deal.”). These two tactics target distinct appraisal dimensions: valence versus significance. We investigated whether these two reappraisals would show similar or different profiles of affective and social effects in the context of close relationship conflicts. Study 1 was based on a sample of 90 Chinese younger adults. Study 2 was based on a sample of 237 American adults (156 MTurk workers and 81 undergraduates combined). Across two studies, both reappraisals effectively improved affect in response to a recalled conflict. Minimising reappraisal group showed significantly increased affect and relationship satisfaction (Study 1&2), but decreased conflict resolution motivation (Study 2) across time. Positive reappraisal group, on the other hand, showed less pronounced increases in positive affect but increased conflict resolution self-efficacy across time (Study 1&2). We discuss these findings by highlighting within-reappraisal variation and potential trade-offs in pursuing affective and social regulation goals.

Tenofovir Alafenamide for Pregnant Chinese Women With Active Chronic Hepatitis B: A Multicenter Prospective Study

Data on long-term tenofovir alafenamide (TAF) therapy for pregnant women with active chronic hepatitis B (CHB) (immune clearance and reactivation phases, currently and previously diagnosed) and their infants are lacking. Pregnant women with active CHB treated with TAF and tenofovir disoproxil fumarate (TDF) were enrolled in this multicenter prospective study, and infants received immunoprophylaxis. The primary outcomes were rates of adverse (safety) events in pregnant women and defects in infants and fetuses. The secondary outcomes were virologic responses in pregnant women, infants' safety, hepatitis B surface antigen (HBsAg) status, and growth conditions. One hundred three and 104 pregnant women were enrolled and 102 and 104 infants were born in the TAF and TDF groups, respectively. In the TAF group, the mean age, gestational age, alanine aminotransferase level, and viral loads at treatment initiation were 29.3 years, 1.3 weeks, 122.2 U/L, and 5.1 log10 IU/mL, respectively. TAF was well-tolerated, and the most common adverse event was nausea (29.1%) during a mean of 2 years of treatment. Notably, 1 (1.0%) TAF-treated pregnant woman underwent induced abortion due to noncausal fetal cleft lip and palate. No infants in either group had birth defects. In the TAF group, the hepatitis B e antigen seroconversion rate was 20.7% at postpartum month 6, infants had normal growth parameters, and no infants were positive for HBsAg at 7 months. The TDF group had comparable safety and effectiveness profiles. TAF administered throughout or beginning in early pregnancy is generally safe and effective for pregnant women with active CHB and their infants.

Concentration-Response Model of Immediate Release Oxycodone Drug Liking by Different Routes of Abuse.

To understand the correlation between oxycodone concentration and drug liking response for immediate-release formulations as they relate to different doses and different routes of administration following manipulation involved in opioid misuse and nontherapeutic use. Concentration-response and noncompartmental analyses of drug liking and plasma oxycodone data from Category 3 human abuse potential studies (n = 15-29 per study) were conducted, using Phoenix 6.0 software. Time to onset of a set threshold of subjective effects (Tonset) and offset of subjective effects (Toffset) were estimated based on a baseline pharmacodynamic response set at 50 on a bipolar Drug Liking visual analog scale of 0-100 and the threshold for drug liking set at ≥65, based on study qualification criteria. Partial Area Under the Concentration (AUCTonset-Toffset) and Effect (AUETonset-Toffset) profiles were calculated and their correlation with individual partial AUE vs partial AUC was assessed. The oxycodone concentration-response (drug liking) was best described by a sigmoidal-effect Emax model (S-shaped). Using a defined threshold, drug liking was closely associated with the rate of rise in concentration and the onset of action for oxycodone administered via oral or intranasal route. Partial AUCTonset-Toffset and AUETonset-Toffset showed a strong linear correlation. Results indicate that oxycodone concentration-response and duration of drug liking following manipulation via different routes of administration may be an approach for further exploring drug liking effects of opioids.

Efficacy and Safety of Lianhuaqingwen Capsules for the Prevention of Coronavirus Disease 2019: A Prospective Open-Label Controlled Trial.

Coronavirus disease 2019 (COVID-19) has become a global pandemic. Community and close contact exposures continue to drive the COVID-19 pandemic. There is no confirmed effective treatment for suspected cases and close contacts. Lianhuaqingwen (LH) capsules, a repurposed Chinese herbal product that is currently on the market, have proven effective for influenza and COVID-19. To determine the safety and efficacy of LH capsules for the prevention of COVID-19, we conducted a prospective open-label controlled trial of LH capsules on subjects who had close contact with people infected with COVID-19. Subjects received LH capsules (4 capsules, three times daily) or the usual medical observation for 14 days. The primary endpoint was the rate of positive nucleic acid tests of nasal and pharyngeal swabs during the quarantine medical observation period. We included 1976 patients, including 1101 in the treatment group and 875 in the control group. The rate of positive nucleic acid tests in the treatment group was significantly lower than that in the control group (0.27% vs. 1.14%, respectively; mean difference: −0.87%; 95% CI: −1.83 to −0.13; p=0.0174) during the quarantine medical observation period (14 days). Among subjects with different close contact states, there was no significant difference in the rate of positive nucleic acid test results among close contacts in the treatment group and the control group (6.45% vs. 11.43%, respectively; p=0.6762). Among secondary close contacts, the rate of positive nucleic acid tests in the treatment group was significantly lower than that in the control group (0.09% vs. 0.71%, respectively; p=0.0485). No serious adverse events were reported. Taken together, and in light of the safety and effectiveness profiles, these results show that LH capsules can be considered to prevent the progression of COVID-19 after close contact with an infected person. This trial is registered with ChiCTR2100043012.

Myocardial protective effect and transcriptome profiling of Naoxintong on cardiomyopathy in zebrafish

BackgroundCardiomyopathy is a kind of cardiovascular diseases, which makes it more difficult for the heart to pump blood to other parts of the body, eventually leading to heart failure. Naoxintong (NXT), as a traditional Chinese Medicine (TCM) preparation, is widely used in the treatment of cardiovascular diseases, including cardiomyopathy, while its underlying mechanism has not been fully elucidated. The purpose of this study is to investigate the therapeutic effect of NXT on cardiomyopathy and its molecular mechanism in zebrafish model.MethodsThe zebrafish cardiomyopathy model was established using terfenadine (TFD) and treated with NXT. The therapeutic effect of NXT on cardiomyopathy was evaluated by measuring the heart rate, the distance between the sinus venosus and bulbus arteriosus (SV-BA), the pericardial area, and the blood flow velocity of zebrafish. Then, the zebrafish hearts were isolated and collected; transcriptome analysis of NXT on cardiomyopathy was investigated. Moreover, the heg1 mutant of zebrafish congenital cardiomyopathy model was used to further validate the therapeutic effect of NXT on cardiomyopathy. Additionally, UPLC analysis combined with the zebrafish model investigation was performed to identify the bioactive components of NXT.ResultsIn the TFD-induced zebrafish cardiomyopathy model, NXT treatment could significantly restore the cardiovascular malformations caused by cardiac dysfunction. Transcriptome and bioinformatics analyses of the TFD and TFD + NXT treated zebrafish developing hearts revealed that the differentially expressed genes were highly enriched in biological processes such as cardiac muscle contraction and heart development. As a cardiac development protein associated with cardiomyopathy, HEG1 had been identified as one of the important targets of NXT in the treatment of cardiomyopathy. The cardiovascular abnormalities of zebrafish heg1 mutant could be recovered significantly from NXT treatment, including the expanded atrial cavity and blood stagnation. qRT-PCR analysis further showed that NXT could restore cardiomyopathy phenotype in zebrafish through HEG1-CCM signaling. Among the seven components identified in NXT, paeoniflorin (PF) and salvianolic acid B (Sal B) were considered to be the main bioactive ones with myocardial protection.ConclusionNXT presented myocardial protective effect and could restore myocardial injury and cardiac dysfunction in zebrafish; the action mechanism was involved in HEG1-CCM signaling.

Selective transepithelial ablation with simultaneous accelerated corneal crosslinking for corneal regularization of keratoconus: STARE-X protocol.

To evaluate the changes in refractive outcomes and corneal aberrations in central and paracentral keratoconus after selective transepithelial topography-guided photorefractive keratectomy combined with accelerated corneal crosslinking (STARE-X). Centro Polispecialistico Mediterraneo, Siena Crosslinking Center, and University of Messina, Italy. Prospective, interventional, multicentric study. Patients were subdivided into 2 groups: Group 1 with cone located within the central 3 mm zone (50 eyes) and Group 2 (50 eyes) with cone located outside the central 3 mm zone. Follow-up was 2 years at least for all eyes. Outcome parameters included uncorrected distance visual acuity (UDVA) and corrected distance visual acuity (CDVA). Corneal tomography and corneal wavefront aberrations were assessed and compared before and 2 years after the treatment. 100 eyes of 100 patients underwent STARE-X protocol. At 2 years, UDVA and CDVA improved, and sphere, cylinder, and Kmax reduced after treatment in both groups (P < .001, respectively). Moreover, a statistically significant reduction was observed of total higher-order aberrations root main square (RMS), coma RMS, and spherical aberration RMS in both groups (P < .001, respectively). However, CDVA improved more in Group 1 than in Group 2 (P < .02). The STARE-X protocol demonstrated effective results in halting keratoconus progression and improving corneal regularity with a safe and effective profile. STARE-X improved both visual acuity and corneal aberration at 2 years. Longer follow-up studies are warranted to observe further long-term CXL flattening effect on the cone.

Ondansetron and metoclopramide as second-line antiemetics in women with nausea and vomiting in pregnancy: the EMPOWER pilot factorial RCT.

Around one-third of pregnant women suffer from moderate to severe nausea and vomiting, causing physical and emotional distress and reducing their quality of life. There is no cure for nausea and vomiting in pregnancy. Management focuses on relieving symptoms and preventing morbidity, and often requires antiemetic therapy. National guidelines make recommendations about first-, second- and third-line antiemetic therapies, although care varies in different hospitals and women report feeling unsupported, dissatisfied and depressed. To determine whether or not, in addition to intravenous rehydration, ondansetron compared with no ondansetron and metoclopramide compared with no metoclopramide reduced the rate of treatment failure up to 10 days after drug initiation; improved symptom severity at 2, 5 and 10 days after drug initiation; improved quality of life at 10 days after drug initiation; and had an acceptable side effect and safety profile. To estimate the incremental cost per treatment failure avoided and the net monetary benefits from the perspectives of the NHS and women. This was a multicentre, double-dummy, randomised, double-blinded, dummy-controlled 2 × 2 factorial trial (with an internal pilot phase), with qualitative and health economic evaluations. Thirty-three patients (who were < 17 weeks pregnant and who attended hospital with nausea and vomiting after little or no improvement with first-line antiemetic medication) who attended 12 secondary care NHS trusts in England, 22 health-care professionals and 21 women participated in the qualitative evaluation. Participants were randomly allocated to one of four treatment groups (1 : 1 : 1: 1 ratio): (1) metoclopramide and dummy ondansetron; (2) ondansetron and dummy metoclopramide; (3) metoclopramide and ondansetron; or (4) double dummy. Trial medication was initially given intravenously and then continued orally once women were able to tolerate oral fluids for a maximum of 10 days of treatment. The primary end point was the number of participants who experienced treatment failure, which was defined as the need for further treatment because symptoms had worsened between 12 hours and 10 days post treatment. The main economic outcomes were incremental cost per additional successful treatment and incremental net benefit. Of the 592 patients screened, 122 were considered eligible and 33 were recruited into the internal pilot (metoclopramide and dummy ondansetron, n = 8; ondansetron and dummy metoclopramide, n = 8; metoclopramide and ondansetron, n = 8; double dummy, n = 9). Owing to slow recruitment, the trial did not progress beyond the pilot. Fifteen out of 30 evaluable participants experienced treatment failure. No statistical analyses were performed. The main reason for ineligibility was prior treatment with trial drugs, reflecting an unpredicted change in prescribing practice at several points along the care pathway. The qualitative evaluation identified the requirements of the study protocol, in relation to guidelines on anti-sickness drugs, and the diversity of pathways to care as key hurdles to recruitment while the role of research staff was a key enabler. No important adverse events or side effects were reported. The pilot trial failed to achieve the recruitment target owing to unforeseen changes in the provision of care. The trial was unable to provide evidence to support clinician decisions about the best choice of second-line antiemetic for nausea and vomiting in pregnancy. Current Controlled Trials ISRCTN16924692 and EudraCT 2017-001651-31. This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 63. See the NIHR Journals Library website for further project information.

Effectiveness and antimicrobial susceptibility profiles during primary antimicrobial prophylaxis for pediatric acute myeloid leukemia

Limited data are available on antimicrobials exposure and microbiology evolution in pediatric acute myeloid leukemia (AML) patients underwent antimicrobials prophylaxis. To assess the effectiveness of antimicrobials prophylaxis, antibiotic susceptibilities of bacteria, and exposure of antimicrobials during intensive chemotherapy for AML patients, 90 consecutive de novo AML patients aged 0–18 years between January 1, 1997 and March 31, 2018 were enrolled. Vancomycin, ciprofloxacin and voriconazole prophylaxis was administered from January 1, 2010. During the preprophylaxis period, January 1997 to December 2009, 62 patients experienced a total of 87 episodes of bloodstream infection (BSI) and 17 episodes of invasive fungal infection (IFI) among 502 courses of chemotherapy. In contrast, 16 episodes of BSI occurred and no IFIs were reported to occur in 28 patients who received 247 courses of chemotherapy in the prophylaxis period. Patients who received antimicrobial prophylaxis had a significant reduction of BSI, IFI, and febrile neutropenia in comparison with patients without prophylaxis. Exposure to amikacin, carbapenem, amphotericin B was reduced in the prophylaxis period. Imipenem susceptibility of Enterobacter cloacae as well as vancomycin susceptibility of Enterococcus species were reduced in the prophylaxis period. At the time of the last follow up, patients with prophylaxis had a better subsequent 5-year overall survival rate than those without prophylaxis. Prophylactic antimicrobials administration in children with AML who undergo chemotherapy can significantly reduce the rates of life-threatening infection, exposure to antimicrobials, and might result in a better outcome.

Пептидрецепторна радіонуклідна терапія гастроентеропанкреатичних нейроендокринних пухлин: профіль ефективності та безпечності використання, критерії вибору методу

Незважаючи на значні успіхи у використанні методів діагностики та лікування, онкологічні захворювання посідають 2-ге місце в структурі смертності, після хвороб системи кровообігу. Хоча традиційні методи лікування злоякісних пухлин, такі як хірургічний, хіміотерапевтичний, променевий, досягли значного розвитку, існують принципові обмеження у ефективності їх ізольованого використання. Особливо це стосується лікування поширених форм онкологічних захворювань на пізніх стадіях. У даній статті проводиться огляд сучасних уявлень про нейроендокринні пухлини шлунково-кишкового тракту та перспективного методу пептидрецепторної радіонуклідної терапії, що базується на ключових даних клінічних досліджень, рекомендацій та інструкції National Comprehensive Cancer Network (NCCN), огляду літератури Lancet Journal, The New England Journal of Medicine, American Society of Clinical Oncology Journal, із використанням пошукового ресурсу PubMed.

Development of a Controlled Continuous Low-Dose Feeding Process

This paper proposes a feed rate control strategy for a novel volumetric micro-feeder, which can accomplish low-dose feeding of pharmaceutical raw materials with significantly different powder properties. The developed feed-forward control strategy enables a constant feed rate with a minimum deviation from the set-point, even for materials that are typically difficult to accurately feed (e.g., due to high cohesion or low density) using conventional continuous feeders. Density variations observed during the feeding process were characterized via a displacement feed factor profile for each powder. The characterized effective displacement density profile was applied in the micro-feeder system to proactively control the feed rate by manipulating the powder displacement rate (i.e., computing the feed rate from the powder displacement rate). Based on the displacement feed factor profile, the feed rate can be predicted during the feeding process and at any feed rate set-point. Three pharmaceutically relevant materials were used for the micro-feeder evaluation: di-calcium phosphate (large-particle system, high density), croscarmellose sodium (small-particle system, medium density), and barium sulfate (very small-particle <10 μm, high density). A significant improvement in the feeding performance was achieved for all investigated materials. The feed rate deviation from the set-point and its relative standard deviation were minimal compared to operations without the control strategy.

Clinical withdrawal symptom profile of synthetic cannabinoid receptor agonists and comparison of effects with high potency cannabis

Synthetic cannabinoid receptor agonists (SCRAs) may be used as an alternative to natural cannabis; however, they may carry a greater risk of problematic use and withdrawal. This study aimed to characterise the withdrawal symptom profile of SCRAs and compare their profile of effect with high-potency herbal cannabis. Global Drug Survey data (2015 and 2016) were used to access a clinically relevant sample of people reporting use of SCRAs >10 times in the past 12-months, a previous SCRA quit attempt, and lifetime use of high-potency herbal cannabis. Participants completed an 11-item SCRA withdrawal symptom checklist and compared SCRAs and high-potency herbal cannabis on their onset and duration of effects, speed of the development of tolerance, severity of withdrawal, and difficulty with dose titration. Participants (n = 284) reported experiencing a mean of 4.4 (95% CI: 4.1, 4.8) withdrawal symptoms after not using SCRAs for >1 day; most frequently reported were sleep issues (59.2%), irritability (55.6%), and low mood (54.2%). Withdrawal symptoms were significantly associated with frequency (>51 vs. 11–50 times per year: IRR = 1.43, 95% CI: 1.16, 1.77, p = 0.005) and quantity (grams per session: IRR = 1.13, 95% CI: 1.05, 1.22, p = 0.001) of SCRA use. Compared to high-potency herbal cannabis, SCRAs were rated as having a faster onset and shorter duration of effects, faster development of tolerance, and more severe withdrawal (p’s < 0.001). In conclusion, SCRA withdrawal symptoms are more likely to occur after greater SCRA exposure. The effects of SCRA indicate a more severe withdrawal syndrome and a greater risk of problematic use than natural cannabis.

Differential Effect of Vaccine Effectiveness and Safety on COVID-19 Vaccine Acceptance across Socioeconomic Groups in an International Sample.

Controlling the spread of SARS-CoV-2 will require high vaccination coverage, but acceptance of the vaccine could be impacted by perceptions of vaccine safety and effectiveness. The aim of this study was to characterize how vaccine safety and effectiveness impact acceptance of a vaccine, and whether this impact varied over time or across socioeconomic and demographic groups. Repeated cross-sectional surveys of an opt-in internet sample were conducted in 2020 in the US, mainland China, Taiwan, Malaysia, Indonesia, and India. Individuals were randomized into receiving information about a hypothetical COVID-19 vaccine with different safety and effectiveness profiles (risk of fever 5% vs. 20% and vaccine effectiveness 50% vs. 95%). We examined the effect of the vaccine profile on vaccine acceptance in a logistic regression model, and included interaction terms between vaccine profile and socioeconomic/demographic variables to examine the differences in sensitivity to the vaccine profile. In total, 12,915 participants were enrolled in the six-country study, including the US (4054), China (2797), Taiwan (1278), Malaysia (1497), Indonesia (1527), and India (1762). Across time and countries, respondents had stronger preferences for a safer and more effective vaccine. For example, in the US in November 2020, acceptance was 3.10 times higher for a 95% effective vaccine with a 5% risk of fever, vs a vaccine 50% effective, with a 20% risk of fever (95% CI: 2.07, 4.63). Across all countries, there was an increase in the effect of the vaccine profile over time (p < 0.0001), with stronger preferences for a more effective and safer vaccine in November 2020 compared to August 2020. Sensitivity to the vaccine profile was also stronger in August compared to November 2020, in younger age groups, among those with lower income; and in those that are vaccine hesitant. Uptake of COVID-19 vaccines could vary in a country based upon effectiveness and availability. Effective communication tools will need to be developed for certain sensitive groups, including young adults, those with lower income, and those more vaccine hesitant.

Effectiveness and Safety of EGFR-TKI Rechallenge Treatment in Elderly Patients with Advanced Non-Small-Cell Lung Cancer Harboring Drug-Sensitive EGFR Mutations.

Background and Objectives: Epidermal growth factor receptor–tyrosine kinase inhibitors (EGFR-TKIs) are effective first-line chemotherapeutic agents for patients with advanced non-small-cell lung cancer (NSCLC) harboring drug-sensitive EGFR mutations. However, the effectiveness of EGFR-TKI rechallenge after first-line EGFR-TKI treatment is not sufficient in elderly patients (over 75 years of age) harboring drug-sensitive EGFR mutations. Therefore, we investigated the effectiveness and safety of EGFR-TKI rechallenge after first-line EGFR-TKI treatment in elderly patients with advanced NSCLC harboring drug-sensitive EGFR mutations. Materials and Methods: Between April 2008 and December 2015, we analyzed 78 elderly patients with advanced NSCLC harboring drug-sensitive EGFR mutations with first-line EGFR-TKI treatment at four Japanese institutions. We retrospectively evaluated the clinical effectiveness and safety profiles of EGFR-TKI rechallenge after first-line EGFR-TKI treatment in elderly patients with advanced NSCLC harboring drug-sensitive EGFR mutations (exon 19 deletion/exon 21 L858R mutation). Results: Twenty-two patients in the cohort were rechallenged with EGFR-TKI. The median age was 79.5 years (range 75–87 years). Despite the fact that it was a retrospective analysis, even with EGFR-TKI rechallenge treatment the response rate was 23%, progression-free survival was 5.3 months, and overall survival was 14.4 months. Common adverse events included rash acneiform, paronychia, diarrhea, and anorexia. There were no treatment-related deaths. Due to the occurrence of adverse events of grade 2 or more, dose reduction was performed in 15 (68.2%) of 22 cases. Conclusions: EGFR-TKI rechallenge treatment after first-line EGFR-TKI treatment in elderly patients with advanced NSCLC harboring drug-sensitive EGFR mutations was one of the limited, safe and effective treatment options for elderly EGFR-positive lung cancer patients.

Comparison of effectiveness and complications in trabeculotomy with phacoemulsification between ab externo and ab interno using a spatula-shaped microhook

To compare the short-term surgical effectiveness and safety profile of trabeculotomy ab externo and ab interno with microhook in terms of the recovery of visual acuity. A retrospective chart review was performed on patients who underwent trabeculotomy combined with phacoemulsification and lens implantation at Asahi General Hospital, with 6 months of follow-up. The patients treated by trabeculotomy were classified into two groups depending on the surgical procedures: ab interno with Tanito microhook (TMH) and ab externo with rigid probe trabeculotome (LOT). The demographics, preoperative and postoperative intraocular pressure (IOP), number of medications (Med), best-corrected visual acuity (BCVA), surgical-induced astigmatism (SIA), and postoperative complications were analyzed at pre-operation, and 1 week and 1–6 months post-operation. Fifty-two eyes of 38 Japanese patients underwent TMH and 42 eyes of 32 patients underwent LOT. The decreases in IOP and Med from the baseline were significant at all time points in both groups (p < 0.001), but there were no significant differences between the two groups. BCVA improved significantly in TMH and LOT after the operation (p < 0.001). BCVA and SIA significantly improved, mostly at 1 week in TMH, compared with LOT (p = 0.02 and 0.003). Hyphema and IOP spike exceeding 30 mmHg (spike) occurred in 11% and 6% of participants in TMH, and 33% and 26% of participants in LOT, respectively. Hyphema and IOP spike occurred more frequently in the LOT than in the TMH group (p = 0.01 and 0.005). Ab interno trabeculotomy showed similar IOP-lowering effects as ab externo, but had less postoperative complications.

Psychosocial interventions for people with a first episode psychosis: between tradition and innovation.

Assessing recent evidence on psychosocial interventions for people with first episode psychosis (FEP). Family interventions (FI) reduce relapse rates, whilst cognitive behavioural therapy (CBT) shows a moderate effect in improving positive psychotic symptoms. Vocational interventions (VI) appear to be worthy of implementation within early intervention for psychosis (EIP) teams, but it is still unclear what is the most cost-effective strategy for their delivery. Promising interventions, which need more careful evaluation, focus on substance misuse, physical health comorbidities, improvement of social participation, peer support and the potential of new technologies. The first five years after the onset of psychotic symptoms are a 'critical period' in which psychosocial interventions can be particularly influential in determining prognosis. Traditional EIP interventions have different effectiveness profiles, i.e., FI reduce relapse rates, CBT has a moderate effectiveness on overall and positive symptoms and VI can improve educational and employment-related functioning. Newer interventions show promise on important targets for FEP treatment but require higher-quality evaluations. Decisions on which interventions to implement within EIP teams should be informed by high-quality evidence, but difficult choices will have to be made based on costs, professionals and technologies available, and local priorities.

Cytokine profile of seminal plasma and effectiveness of assisted reproductive technology programs

Increasing evidence shows that seminal plasma is among the most important immunoregulatory factors in female reproductive function. We suggest that the favorable effect of the partner’s seminal plasma (SP) upon pregnancy occurence in women during the cycle of in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) may be provided by the balanced content of Th1/Th2-dependent seminal cytokines. Otherwise, in case of pathologic changes in SP composition, it may negatively affect the IVF efficiency. Our aim was to determine whether the levels of seminal IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-18, IFNγ, TNFα, TNFβ and TGF-β1 are associated with pregnancy establishment in female patients exposed to seminal plasma during IVF/ICSI cycle.Twenty-eight female patients were exposed to seminal plasma via sexual intercourse before the day of oocyte retrieval, and also underwent intravaginal application of seminal plasma just after transvaginal puncture and oocyte retrieval. Quantitative measurement of seminal cytokines was performed by FlowCytomix™ technology. IL-1, IL-18 and TNFβ concentrations were significantly higher in non-pregnant group (p = 0.011; p = 0.030 and p = 0.008, respectively). The contents of IL-2, IL-6, IL-18 and TNFβ per ejaculate were also significantly higher in non-pregnant group (p = 0.020; р = 0.042; р = 0.030 and р = 0.004, respectively). We conclude that elevated concentrations of proinflammatory cytokines in seminal plasma, as well as their total excessive content per ejaculate may have an adverse effect on implantation and pregnancy establishment.

A Prospective Study of Intraarterial Infusion Chemotherapy in Advanced Wild-Type BRAF Melanoma Patients

Treatment strategies for advanced cutaneous melanoma (CM) patients, resistant or not treatable with novel target and immunotherapeutic drugs, remain a significant challenge, particularly for patients with unresectable stage IIIC/D disease localized to inferior limbs and pelvis, for whom specific outcomes are rarely considered. This is a prospective study of multidisciplinary treatments, including locoregional melphalan chemotherapy, in 62 BRAF wild-type CM patients with locoregional metastases in the inferior limbs and pelvis, including inguinal regions. Patients were either in progression following or ineligible for, or not treatable with novel immunotherapy. For exclusively inferior limb-localised disease, patients received locoregional melphalan chemotherapy performed by hyperthermic isolated limb perfusion (n=19) or isolated limb infusion (n=19), and for synchronous lesions localised to inferior limbs and pelvis, received hypoxic pelvic and limb perfusion (n=24). Additional multidisciplinary therapy included local, locoregional and systemic treatments and the primary endpoint was tumour response. The objective response rate following first cycle of locoregional chemotherapy was 37.1% at 3 mo and median progression-free survival was 4-mo, with 12.9% procedure-related complications, 30.6% low-grade haematological toxicity and 11.3% severe limb toxic tissue reactions. Multivariate logistic regression showed that the odds of response were significantly higher for patients ≤ 75 y of age and for patients with locoregional metastases exclusively located in the inferior limbs. In this subgroup of CM patients with BRAF wild-type status, locoregional metastases localized to inferior limbs and pelvis, in progression following or ineligible for immunotherapy, melphalan locoregional chemotherapy demonstrated a safe and effective profile. ClinicalTrials.gov Identifier NCT01920516; date of trial registration: August 6, 2013.

Vaccine Hesitancy and Rejection of a Vaccine for the Novel Coronavirus in the United States.

The arrival of the COVID-19 vaccine has been accompanied by increased discussion of vaccine hesitancy. However, it is unclear if there are shared patterns between general vaccine hesitancy and COVID-19 vaccine rejection, or if these are two different concepts. This study characterized rejection of a hypothetical COVID-19 vaccine, and compared patterns of association between general vaccine hesitancy and COVID-19 vaccine rejection. The survey was conducted online March 20-22, 2020. Participants answered questions on vaccine hesitancy and responded if they would accept the vaccine given different safety and effectiveness profiles. We assessed differences in COVID-19 rejection and general vaccine hesitancy through logistic regressions. Among 713 participants, 33.0% were vaccine hesitant, and 18.4% would reject a COVID-19 vaccine. Acceptance varied by effectiveness profile: 10.2% would reject a 95% effective COVID-19 vaccine, but 32.4% would reject a 50% effective vaccine. Those vaccine hesitant were significantly more likely to reject COVID-19 vaccination [odds ratio (OR): 5.56, 95% confidence interval (CI): 3.39, 9.11]. In multivariable logistic regression models, there were similar patterns for vaccine hesitancy and COVID-19 vaccine rejection by gender, race/ethnicity, family income, and political affiliation. But the direction of association flipped by urbanicity (P=0.0146, with rural dwellers less likely to be COVID-19 vaccine rejecters but more likely to be vaccine hesitant in general), and age (P=0.0037, with fewer pronounced differences across age for COVID-19 vaccine rejection, but a gradient of stronger vaccine hesitancy in general among younger ages). During the COVID-19 epidemic’s early phase, patterns of vaccine hesitancy and COVID-19 vaccine rejection were relatively similar. A significant minority would reject a COVID-19 vaccine, especially one with less-than-ideal effectiveness. Preparations for introducing the COVID-19 vaccine should anticipate substantial hesitation and target concerns, especially among younger adults.