An ancestral axial twist explains the contralateral forebrain and the optic chiasm in vertebrates

Among the best-known facts of the brain are the contralateral visual, auditory, sensational, and motor mappings in the forebrain. How and why did these evolve? The few theories to this question provide functional answers, such as better networks for visuomotor control. However, these theories contradict the data, as discussed here. Instead we propose that a 90-deg left-turn around the body-axis evolved in a common ancestor of all vertebrates. Compensatory migrations of the tissues during development restore body symmetry. Eyes, nostrils and forebrain compensate in the direction of the turn, whereas more caudal structures migrate in the opposite direction. As a result of these opposite migrations the forebrain becomes crossed and inverted with respect to the rest of the nervous system. We show that these compensatory migratory movements can indeed be observed in the zebrafish (Danio rerio) and the chick (Gallus gallus). With a model we show how the axial twist hypothesis predicts that an optic chiasm should develop on the ventral side of the brain, whereas the olfactory tract should be uncrossed. In addition, the hypothesis explains the decussation of the trochlear nerve, why olfaction is non-crossed, why the cerebellar hemispheres represent the ipsilateral bodyside, why in sharks the forebrain halves each represent the ipsilateral eye, why the heart and other inner organs are asymmetric in the body. Due to the poor fossil record, the possible evolutionary scenarios remain speculative. Molecular evidence does support the hypothesis. The findings may throw new insight on the problematic structure of the forebrain.Comment: 13 pages, 6 figures. A small correction is made (May 2014): see footnote

Diversification of prey capture techniques among the piscivores in Lake Tana's (Ethiopia) Labeobarbus species flock (Cyprinidae)

Lake Tana harbours the only known intact species flock of large cyprinid fishes (15 Labeobarbus spp.). One of the most curious aspects of this species flock is the large number (8) of piscivorous species. Cyprinids are not well designed for piscivory (i.e. small slit-shaped pharyngeal cavity, lack of teeth in the oral jaws, lack of a stomach), which raises the question how well adapted these labeobarbs actually are to function as piscivores? In this study we analyse the kinematics of prey capture (by varied combinations of suction, swimming and jaw protrusion) among Lake Tana's piscivorous labeobarbs. Suction feeding kinematics were similar to values reported for other piscivorous fish species. A detailed analysis of several Labeobarbus species displayed distinct types of techniques (overswimming, velocity/volume suction with jaw protrusion) suited to capture elusive prey in different macro-habitats, Lake Tana's Labeobarbus species evolved a wide range of piscivorous predation techniques, a unique scenario for cyprinid fishes

Knowledge-Attitudes-Practices About Malaria Among Communities in Southern Benin

Malaria still remains the main public health problem in Benin. We explored the determinants that influenced malaria treatment as well as protective behaviors, to generate a framework of useful ideas as alternative strategies against malaria. A cross-sectional survey of the knowledge, attitudes and practices (KAP) was conducted at Hozin, Vakon and Agblangandan districts in southern region of Benin. Descriptive statistics were computed and mixed logistic regression helped evaluating the relationship between frequency of each category of severity of malaria and sex group, educational level, treatment, means of self-protection against mosquitoes and identification of the cause of malaria. A significant proportion 750 (81.3%) (p<0.001) of participants stated that malaria was caused by mosquitoes. The respondents who mentioned sun as the cause of malaria, have trivialized more malaria in a proportion of about 59.30% (OR=2.67 [95% CI 1.61-4.44]) followed by those who have reported the cause of body weakness (43.68%) (OR=2.97 [95% CI 1.68-5.28]). Poor knowledge justifies the trivialization of the disease and poor management of malaria control means. National Malaria Control Programs should improve access to education, especially for women and could help improving prevention and control behaviours against malaria in communities

Comparing Single-Incision Midurethral Sling with Bulking Agents for Female Stress Urinary Incontinence:Rationale for a Non-Randomized Controlled Trial

Objectives: Midurethral slings are considered the gold standard for the surgical treatment of stress urinary incontinence (SUI), with an efficacy up to 80%. Another therapeutic option is the use of bulking agents, which create an artificial mass in the urethral submucosa, with an efficacy varying from 64% to 74%. Although bulking agents have a lower risk of complications than midurethral sling surgery, they are mainly used in case a midurethral sling is not an option or if midurethral sling surgery failed to cure stress urinary incontinence. In this study, we offer all patients with SUI in secondary care a choice between a single-incision midurethral sling procedure and treatment with a bulking agent. We want to examine patient preference and patient satisfaction for both procedures. We expect that offering both interventions in combination with standardized counselling will result in high patient satisfaction. Design: In this non-randomized controlled trial, 266 patients will be objectively counselled for both interventions, after which all patients will choose between single-incision midurethral slings and polyacrylamide hydrogel (PAHG), followed by the standard care procedure for women with SUI. Participants/Materials, Setting, Methods: From January 1, 2021, onward, all consecutive adult patients (between 18 and 80 years of age) attending the outpatient gynaecology department with objectively confirmed, moderate to severe SUI will be eligible for enrolment in this non-randomized study. The primary outcome is patient satisfaction at 1 year, measured by the Patient Global Impression of Improvement; secondary outcomes are patient satisfaction at 3 months, objective and subjective cure at 3 months and 1 year, adverse events, post-operative pain, and cost-effectiveness. Differences in outcome measures will be assessed through logistic and linear regression analyses, both unadjusted and adjusted with covariate adjustment using the propensity score. Results: No results are available yet. Limitations: The major disadvantage of this study design is the potential confounding bias. We intend to eliminate this bias by applying propensity scoring. Conclusion: By designing a non-randomized patient preference trial, we not only expect to demonstrate high patient satisfaction with both interventions but also provide insight into the possible role of PAHG-injections in the treatment of female SUI as a first-choice non-conservative treatment.</p

Music to prevent deliriUm during neuroSurgerY (MUSYC) Clinical trial:A study protocol for a randomised controlled trial

INTRODUCTION: Delirium is a neurocognitive disorder characterised by an acute and temporary decline of mental status affecting attention, awareness, cognition, language and visuospatial ability. The underlying pathophysiology is driven by neuroinflammation and cellular oxidative stress. Delirium is a serious complication following neurosurgical procedures with a reported incidence varying between 4% and 44% and has been associated with increased length of hospital stay, increased amount of reoperations, increased costs and mortality. Perioperative music has been reported to reduce preoperative anxiety, postoperative pain and opioid usage, and attenuates stress response caused by surgery. We hypothesize that this beneficial effect of music on a combination of delirium eliciting factors might reduce delirium incidence following neurosurgery and subsequently improve clinical outcomes. METHODS: This protocol concerns a single-centred prospective randomised controlled trial with 6 months follow-up. All adult patients undergoing a craniotomy at the Erasmus Medical Center in Rotterdam are eligible. The music group will receive recorded music through an overear headphone before, during and after surgery until postoperative day 3. Patients can choose from music playlists, offered based on music importance questionnaires administered at baseline. The control group will receive standard of clinical care Delirium is assessed by the Delirium Observation Scale and confirmed by a delirium-expert psychiatrist according to the DSM-5 criteria. Risk factors correlated with the onset of delirium, such as cognitive function at baseline, preoperative anxiety, perioperative medication use, depth of anaesthesia and postoperative pain, and delirium-related health outcomes such as length of stay, daily function, quality of life (ie, EQ-5D, EORTC questionnaires), costs and cost-effectiveness are collected. ETHICS AND DISSEMINATION: This study is being conducted in accordance with the Declaration of Helsinki. The Medical Ethics Review Board of Erasmus University Medical Center Rotterdam, The Netherlands, approved this protocol. Results will be disseminated via peer-reviewed scientific journals and conference presentations. TRIAL REGISTRATION NUMBERS: NL8503 and NCT04649450

Perspectives of patients, relatives and nurses on rooming-in for adult patients: A scoping review of the literature

Aim: To explore the perspectives of patients, their relatives and nurses on rooming-in for adult patients. Background: The practice of having family stay overnight with an adult patient in hospital is quite new. To support rooming-in programs, the perspectives from all stakeholders should be taken into account. Methods: All types of studies on rooming-in in adult healthcare settings were included in this scoping review. Rooming-in has been defined as the practice where ‘family members or trusted others are facilitated to continuously stay with the patient and are provided with facilities to sleep in the patient's room’. Results: Seven studies were included: one randomized controlled trial, three qualitative studies, and three correspondence articles. Generally, patients felt safe in the presence of a family member, but could also feel restricted in their freedom and privacy. Family members saw a benefit for the patient, considered rooming-in a moral duty, and were happy to help. Nonetheless, family members reported rooming-in as physically and emotionally stressful. Nurses described that patients were less anxious and more easily adjusted to the hospital environment. Conclusions: The reviewed studies suggest that patients, family members, and nurses have both positive and negative experiences with rooming-in. The concept

Intradermal lipopolysaccharide challenge as an acute in vivo inflammatory model in healthy volunteers

Aims: Whereas intravenous administration of Toll-like receptor 4 ligand lipopolysaccharide (LPS) to human volunteers is frequently used in clinical pharmacology studies, systemic use of LPS has practical limitations. We aimed to characterize the intradermal LPS response in healthy volunteers, and as such qualify the method as local inflammation model for clinical pharmacology studies. Methods: Eighteen healthy male volunteers received 2 or 4 intradermal 10 ng LPS injections and 1 saline injection on the forearms. The LPS response was evaluated by noninvasive (perfusion, skin temperature and erythema) and invasive assessments (cellular and cytokine responses) in skin biopsy and blister exudate. Results: LPS elicited a visible response and returned to baseline at 48 hours. Erythema, perfusion and temperature were statistically significant (P < .0001) over a 24-hour time course compared to saline. The protein response was dominated by an acute interleukin (IL)-6, IL-8 and tumour necrosis factor response followed by IL-1β, IL-10 and interferon-γ. The cellular response consisted of an acute neutrophil influx followed by different monocyte subsets and dendritic cells. Discussion: Intradermal LPS administration in humans causes an acute, localized and transient inflammatory reaction that is well-tolerated by healthy volunteers. This may be a valuable inflammation model for evaluating the pharmacological activity of anti-inflammatory investigational compounds in proof of pharmacology studies

Efficacy of haloperidol to decrease the burden of delirium in adult critically ill patients:the EuRIDICE randomized clinical trial

Background:The role of haloperidol as treatment for ICU delirium and related symptoms remains controversial despite two recent large controlled trials evaluating its efficacy and safety. We sought to determine whether haloperidol when compared to placebo in critically ill adults with delirium reduces days with delirium and coma and improves delirium-related sequelae.Methods:This multi-center double-blind, placebo-controlled randomized trial at eight mixed medical-surgical Dutch ICUs included critically ill adults with delirium (Intensive Care Delirium Screening Checklist ≥ 4 or a positive Confusion Assessment Method for the ICU) admitted between February 2018 and January 2020. Patients were randomized to intravenous haloperidol 2.5 mg or placebo every 8 h, titrated up to 5 mg every 8 h if delirium persisted until ICU discharge or up to 14 days. The primary outcome was ICU delirium- and coma-free days (DCFDs) within 14 days after randomization. Predefined secondary outcomes included the protocolized use of sedatives for agitation and related behaviors, patient-initiated extubation and invasive device removal, adverse drug associated events, mechanical ventilation, ICU length of stay, 28-day mortality, and long-term outcomes up to 1-year after randomization.Results:The trial was terminated prematurely for primary endpoint futility on DSMB advice after enrolment of 132 (65 haloperidol; 67 placebo) patients [mean age 64 (15) years, APACHE IV score 73.1 (33.9), male 68%]. Haloperidol did not increase DCFDs (adjusted RR 0.98 [95% CI 0.73–1.31], p = 0.87). Patients treated with haloperidol (vs. placebo) were less likely to receive benzodiazepines (adjusted OR 0.41 [95% CI 0.18–0.89], p = 0.02). Effect measures of other secondary outcomes related to agitation (use of open label haloperidol [OR 0.43 (95% CI 0.12–1.56)] and other antipsychotics [OR 0.63 (95% CI 0.29–1.32)], self-extubation or invasive device removal [OR 0.70 (95% CI 0.22–2.18)]) appeared consistently more favorable with haloperidol, but the confidence interval also included harm. Adverse drug events were not different. Long-term secondary outcomes (e.g., ICU recall and quality of life) warrant further study.Conclusions:Haloperidol does not reduce delirium in critically ill delirious adults. However, it may reduce rescue medication requirements and agitation-related events in delirious ICU patients warranting further evaluation.Trial registration: ClinicalTrials.gov (#NCT03628391), October 9, 2017

The landscape of somatic mutations in Indonesian cervical cancer is predominated by the PI3K pathway

Molecular tumour pathology - and tumour genetic