Study on the formation of nitrogenous disinfection by products from the reaction between dichloroacetaldehyde and monochloramine

Disinfection is a mandatory step in drinking water treatment to inactivate harmful pathogens found in source waters and minimize health risks for human consumers. Among many powerful oxidants commonly used as disinfectants, chlorine has been widely utilized at many water treatment facilities due to low cost and high efficiency in reducing waterborne diseases such as cholera and typhoid. However, the major downside of this process is the formation of a group of compounds known as disinfection by-products (DBPs) when chlorine unintentionally reacts with some constituents naturally occurring in source water. To prevent the negative health effects of chlorinated DBPs such as trihalomethanes (THMs) and haloacetic acids (HAAs), regulations that stipulate their maximum contaminant levels have been established since 1970s and gradually become more stringent. For this reason, switching to alternative disinfectants (i.e. ozone, UV or chloramine) helps to significantly reduce the concentration of chlorinated DBPs in finished water. Although this strategy allows water utilities to comply the stricter regulation recently proposed, the alternative disinfectants introduce new DBP classes that are not well studied and can also cause severe human health effects. Among newly found DBPs which are introduced to disinfected water by using alternative disinfectant, nitrogen containing DBPs (N-DBPs) are of growing concern to human consumers due to their relatively high toxicity compared to regulated DBPs mostly produced by chlorination. Occurrence studies have shown that haloacetonitriles (HANs) and haloacetamides (HAMs), two unregulated N-DBP groups, were commonly found in drinking water with chloramine disinfection. Although these N-DBP groups occur at lower levels than chlorinated DBPs, they are shown to be more toxic and can significantly contribute to the overall toxicity of disinfected drinking water. In addition, haloaldehydes were also observed in the finished water from several water facilities and they are identified as the third largest DBP group by weight, only behind THMs and HAAs. For the first time, this study confirms the predominant formation of HAN and HAM dominant species, dichloroacetonitrile (DCAN) and dichloroacetamide (DCAM), from the reaction between monochloramine and dichloroacetaldehyde via the aldehyde reaction pathway. Initial reactants reacted quickly and reached equilibrium with carbinolamine 2,2-dichloro-1-(chloroamino)ethanol. Then, the carbinolamine underwent two parallel reactions where, (1) it slowly dehydrated to 1,1-dichloro-2-(chloroimino)ethane and further decomposed to dichloroacetonitrile and (2) it was oxidized by monochloramine to form a newly discovered N-haloacetamide N,2,2-trichloroacetamide. Additionally, labelled 15N-monochloramine experiments with natural water reveals the prevalence of the aldehyde pathway in real drinking water conditions as 60-70% DCAN and DCAM contain 15N atom which was contributed by 15N-monochloramine. Furthermore, free chlorine pretreatment followed by chloramination was shown to enhance the formation of 15N-DBPs. A kinetic model was developed that predicted up to 90% of N-DBPs in natural waters

Safety and efficacy of fluoxetine on functional outcome after acute stroke (AFFINITY): a randomised, double-blind, placebo-controlled trial

Background Trials of fluoxetine for recovery after stroke report conflicting results. The Assessment oF FluoxetINe In sTroke recoverY (AFFINITY) trial aimed to show if daily oral fluoxetine for 6 months after stroke improves functional outcome in an ethnically diverse population. Methods AFFINITY was a randomised, parallel-group, double-blind, placebo-controlled trial done in 43 hospital stroke units in Australia (n=29), New Zealand (four), and Vietnam (ten). Eligible patients were adults (aged ≥18 years) with a clinical diagnosis of acute stroke in the previous 2–15 days, brain imaging consistent with ischaemic or haemorrhagic stroke, and a persisting neurological deficit that produced a modified Rankin Scale (mRS) score of 1 or more. Patients were randomly assigned 1:1 via a web-based system using a minimisation algorithm to once daily, oral fluoxetine 20 mg capsules or matching placebo for 6 months. Patients, carers, investigators, and outcome assessors were masked to the treatment allocation. The primary outcome was functional status, measured by the mRS, at 6 months. The primary analysis was an ordinal logistic regression of the mRS at 6 months, adjusted for minimisation variables. Primary and safety analyses were done according to the patient's treatment allocation. The trial is registered with the Australian New Zealand Clinical Trials Registry, ACTRN12611000774921. Findings Between Jan 11, 2013, and June 30, 2019, 1280 patients were recruited in Australia (n=532), New Zealand (n=42), and Vietnam (n=706), of whom 642 were randomly assigned to fluoxetine and 638 were randomly assigned to placebo. Mean duration of trial treatment was 167 days (SD 48·1). At 6 months, mRS data were available in 624 (97%) patients in the fluoxetine group and 632 (99%) in the placebo group. The distribution of mRS categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio 0·94, 95% CI 0·76–1·15; p=0·53). Compared with patients in the placebo group, patients in the fluoxetine group had more falls (20 [3%] vs seven [1%]; p=0·018), bone fractures (19 [3%] vs six [1%]; p=0·014), and epileptic seizures (ten [2%] vs two [<1%]; p=0·038) at 6 months. Interpretation Oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and epileptic seizures. These results do not support the use of fluoxetine to improve functional outcome after stroke

Acetonitrile and <i>N</i>‑Chloroacetamide Formation from the Reaction of Acetaldehyde and Monochloramine

Nitriles and amides are two classes of nitrogenous disinfection byproducts (DBPs) associated with chloramination that are more cytotoxic and genotoxic than regulated DBPs. Monochloramine reacts with acetaldehyde, a common ozone and free chlorine disinfection byproduct, to form 1-(chloroamino)­ethanol. Equilibrium (<i>K</i>₁) and forward and reverse rate (<i>k</i>₁,<i>k</i>_–1) constants for the reaction between initial reactants and 1-(chloroamino)­ethanol were determined between 2 and 30 °C. Activation energies for <i>k</i>₁ and <i>k</i>_–1 were 3.04 and 45.2 kJ·mol^–1, respectively, and enthalpy change for <i>K</i>₁ was −42.1 kJ·mol^–1. In parallel reactions, 1-(chloroamino)­ethanol (1) slowly dehydrated (<i>k</i>₂) to (chloroimino)­ethane that further decomposed to acetonitrile and (2) was oxidized (<i>k</i>₃) by monochloramine to produce <i>N</i>-chloroacetamide. Both reactions were acid/base catalyzed, and rate constants were characterized at 10, 18, and 25 °C. Modeling for drinking water distribution system conditions showed that <i>N</i>-chloroacetamide and acetonitrile concentrations were 5–9 times higher at pH 9.0 compared to 7.8. Furthermore, acetonitrile concentration was found to form 7–10 times higher than <i>N</i>-chloroacetamide under typical monochloramine and acetaldehyde concentrations. <i>N</i>-chloroacetamide cytotoxicity (LC₅₀ = 1.78 × 10^–3 M) was comparable to dichloroacetamide and trichloroacetamide, but less potent than <i>N</i>,2-dichloroacetamide and chloroacetamide. While <i>N</i>-chloroacetamide was not found to be genotoxic, <i>N</i>,2-dichloroacetamide genotoxic potency (5.19 × 10^–3 M) was on the same order of magnitude as chloroacetamide and trichloroacetamide

Tinctoric acid A-B, two new hopan-type triterpenoids from the Vietnamese lichen, <i>Parmotrema tinctorum</i> (Despr. ex Nyl.) hale with α-glucosidase inhibitory activity

Two new hopan-type triterpenoids, namely tinctoric acid A-B (1-2), were isolated from the lichen Parmotrema tinctorum (Despr. ex Nyl.) Hale. Their structures were elucidated by extensive spectroscopic analyses (1D and 2D NMR). The absolute configuration at C-22 of 1 was established through DP4 probability. Compounds 1-2 were evaluated for their inhibitory activity against α-glucosidase and found to be more potent than those of positive control (acarbose, IC50 168 µM) with values IC50 74.7 and 98.2 µM, respectively. Both of these compounds interacted well with enzyme α-glucosidase MAL32 through H-bonds and hydrophobic interaction.</p

Population-Based Incidence Rates of First- Ever Stroke in Central Vietnam

Abstract Introductio

Twelve-Month Outcomes of the AFFINITY Trial of Fluoxetine for Functional Recovery After Acute Stroke: AFFINITY Trial Steering Committee on Behalf of the AFFINITY Trial Collaboration

Background and Purpose: The AFFINITY trial (Assessment of Fluoxetine in Stroke Recovery) reported that oral fluoxetine 20 mg daily for 6 months after acute stroke did not improve functional outcome and increased the risk of falls, bone fractures, and seizures. After trial medication was ceased at 6 months, survivors were followed to 12 months post-randomization. This preplanned secondary analysis aimed to determine any sustained or delayed effects of fluoxetine at 12 months post-randomization. Methods: AFFINITY was a randomized, parallel-group, double-blind, placebo-controlled trial in adults (n=1280) with a clinical diagnosis of stroke in the previous 2 to 15 days and persisting neurological deficit who were recruited at 43 hospital stroke units in Australia (n=29), New Zealand (4), and Vietnam (10) between 2013 and 2019. Participants were randomized to oral fluoxetine 20 mg once daily (n=642) or matching placebo (n=638) for 6 months and followed until 12 months after randomization. The primary outcome was function, measured by the modified Rankin Scale, at 6 months. Secondary outcomes for these analyses included measures of the modified Rankin Scale, mood, cognition, overall health status, fatigue, health-related quality of life, and safety at 12 months. Results: Adherence to trial medication was for a mean 167 (SD 48) days and similar between randomized groups. At 12 months, the distribution of modified Rankin Scale categories was similar in the fluoxetine and placebo groups (adjusted common odds ratio, 0.93 [95% CI, 0.76–1.14]; P =0.46). Compared with placebo, patients allocated fluoxetine had fewer recurrent ischemic strokes (14 [2.18%] versus 29 [4.55%]; P =0.02), and no longer had significantly more falls (27 [4.21%] versus 15 [2.35%]; P =0.08), bone fractures (23 [3.58%] versus 11 [1.72%]; P =0.05), or seizures (11 [1.71%] versus 8 [1.25%]; P =0.64) at 12 months. Conclusions: Fluoxetine 20 mg daily for 6 months after acute stroke had no delayed or sustained effect on functional outcome, falls, bone fractures, or seizures at 12 months poststroke. The lower rate of recurrent ischemic stroke in the fluoxetine group is most likely a chance finding. REGISTRATION: URL: http://www.anzctr.org.au/ ; Unique identifier: ACTRN12611000774921