Achieving global biodiversity goals by 2050 requires urgent and integrated actions

Governments are negotiating actions intended to halt biodiversity loss and put it on a path to recovery by 2050. Here, we show that bending the curve for biodiversity is possible, but only if actions are implemented urgently and in an integrated manner. Connecting these actions to biodiversity outcomes and tracking progress remain a challenge

Genetic Testing to Inform Epilepsy Treatment Management From an International Study of Clinical Practice

IMPORTANCE: It is currently unknown how often and in which ways a genetic diagnosis given to a patient with epilepsy is associated with clinical management and outcomes. OBJECTIVE: To evaluate how genetic diagnoses in patients with epilepsy are associated with clinical management and outcomes. DESIGN, SETTING, AND PARTICIPANTS: This was a retrospective cross-sectional study of patients referred for multigene panel testing between March 18, 2016, and August 3, 2020, with outcomes reported between May and November 2020. The study setting included a commercial genetic testing laboratory and multicenter clinical practices. Patients with epilepsy, regardless of sociodemographic features, who received a pathogenic/likely pathogenic (P/LP) variant were included in the study. Case report forms were completed by all health care professionals. EXPOSURES: Genetic test results. MAIN OUTCOMES AND MEASURES: Clinical management changes after a genetic diagnosis (ie, 1 P/LP variant in autosomal dominant and X-linked diseases; 2 P/LP variants in autosomal recessive diseases) and subsequent patient outcomes as reported by health care professionals on case report forms. RESULTS: Among 418 patients, median (IQR) age at the time of testing was 4 (1-10) years, with an age range of 0 to 52 years, and 53.8% (n = 225) were female individuals. The mean (SD) time from a genetic test order to case report form completion was 595 (368) days (range, 27-1673 days). A genetic diagnosis was associated with changes in clinical management for 208 patients (49.8%) and usually (81.7% of the time) within 3 months of receiving the result. The most common clinical management changes were the addition of a new medication (78 [21.7%]), the initiation of medication (51 [14.2%]), the referral of a patient to a specialist (48 [13.4%]), vigilance for subclinical or extraneurological disease features (46 [12.8%]), and the cessation of a medication (42 [11.7%]). Among 167 patients with follow-up clinical information available (mean [SD] time, 584 [365] days), 125 (74.9%) reported positive outcomes, 108 (64.7%) reported reduction or elimination of seizures, 37 (22.2%) had decreases in the severity of other clinical signs, and 11 (6.6%) had reduced medication adverse effects. A few patients reported worsening of outcomes, including a decline in their condition (20 [12.0%]), increased seizure frequency (6 [3.6%]), and adverse medication effects (3 [1.8%]). No clinical management changes were reported for 178 patients (42.6%). CONCLUSIONS AND RELEVANCE: Results of this cross-sectional study suggest that genetic testing of individuals with epilepsy may be materially associated with clinical decision-making and improved patient outcomes

Epidemiology and management of chronic constipation in elderly patients

Maria Vazquez Roque, Ernest P Bouras Gastroenterology and Hepatology Department, Mayo Clinic, Jacksonville, FL, USA Abstract: Constipation is a common functional gastrointestinal disorder, with prevalence in the general population of approximately 20%. In the elderly population the incidence of constipation is higher compared to the younger population, with elderly females suffering more often from severe constipation. Treatment options for chronic constipation (CC) include stool softeners, fiber supplements, osmotic and stimulant laxatives, and the secretagogues lubiprostone and linaclotide. Understanding the underlying etiology of CC is necessary to determine the most appropriate therapeutic option. Therefore, it is important to distinguish from pelvic floor dysfunction (PFD), slow and normal transit constipation. Evaluation of a patient with CC includes basic blood work, rectal examination, and appropriate testing to evaluate for PFD and slow transit constipation when indicated. Pelvic floor rehabilitation or biofeedback is the treatment of choice for PFD, and its efficacy has been proven in clinical trials. Surgery is rarely indicated in CC and can only be considered in cases of slow transit constipation when PFD has been properly excluded. Other treatment options such as sacral nerve stimulation seem to be helpful in patients with urinary dysfunction. Botulinum toxin injection for PFD cannot be recommended at this time with the available evidence. CC in the elderly is common, and it has a significant impact on quality of life and the use of health care resources. In the elderly, it is imperative to identify the etiology of CC, and treatment should be based on the patient’s overall clinical status and capabilities. Keywords: pelvic floor dysfunction, constipation, elderly&nbsp

On the Microporous Nature of Transition Metal Nitroprussides

Nitroprussides of divalent transition metals form a family of microporous molecular materials. Their properties in this sense depend on the transition metal cation involved and also on the preparative method, which determine their crystal structures. The stable phases of this family of materials belong to one of the following crystal structures: orthorhombic (Pnma) (Mn2+, Fe2+, Cu2+, Zn2+, and Cd2+), cubic (Fm3m) (Co2+ and Ni2+), and orthorhombic (Amm2) (Cu2+). These materials are stable up to above 160 °C, while their dehydration takes place around 100 °C. On dehydration, Amm2 copper complex changes into a tetragonal (I4mm) phase. The microporous nature of these materials is discussed according to their crystal structure and correlating structural and adsorption data. The accessibility to the pore system was evaluated through adsorption of H2O, CO2, and N2. Pores of both orthorhombic and cubic structures are accessible to H2O and CO2 in experiments carried out at 23 and 0 °C, respectively; however, they are inaccessible to N2 at -196 °C. This behavior is discussed as related to the large polarizing power of the nitrosyl (NO) ligand which distorts the local environment of the iron atom and reduces the effective window cross section. The small pores of tetragonal copper nitroprusside were inaccessible to the adsorbates used

Pharmacodynamic effects of a novel prokinetic 5-HT4receptor agonist, ATI-7505, in humans

ATI-7505, an investigational 5-HT4 receptor agonist, was designed to have similar activity as cisapride without the cardiac adverse effects, i.e. without QT prolongation. In addition, ATI-7505 is not metabolized by CYP450. The aim of the study was to assess the effect of ATI-7505 on gastrointestinal (GI) and colonic transit in healthy humans. A randomized, parallel-group, double-blind, placebo-controlled study evaluated effects of 9-day treatment with ATI-7505 (3, 10 or 20 mg t.i.d.) on scintigraphic GI and colonic transit in healthy volunteers (12 per group). Primary endpoints were gastric-emptying (GE) T1/2, colonic geometric centre (GC) at 24 h and ascending colon (AC) emptying T1/2. Daily stool diaries were kept. Analysis of covariance assessed overall treatment group differences, followed by post hoc unadjusted pairwise comparisons. There were borderline overall treatment effects (decrease) on GE T1/2 (P = 0.154); the 20 mg t.i.d. of ATI-7505-accelerated GE vs placebo (P = 0.038). ATI-7505 increased colonic transit (GC24, P = 0.031) with fastest transit at 10 mg t.i.d. vs placebo (P = 0.065). ATI-7505 accelerated AC emptying T1/2 (overall P = 0.075) with 10 mg dose vs placebo (P = 0.042). There was looser stool (Bristol stool form scale, overall P = 0.056) with the 10 and 20 mg t.i.d. doses. No safety issues were identified. ATI-7505 accelerates overall colonic transit and tends to accelerate GE and AC emptying and loosen stool consistency