atropine + pralidoxime chloride (Duodote)

Pretreatment myopia progression is associated with the response to 0.01% atropine: a post-hoc secondary analysis of a randomized controlled trial.

Wei Shi-Fei SF, Bai Wei-Ling WL, Sun Yun-Yun YY, An Wen-Zai WZ et al.

To determine which subgroup of children would best benefit from 0.01% atropine eyedrop. This post hoc secondary analysis assessed 68 subjects. Placebo for the first year and 0.01% atropine eye drops for the second year. According to the annual spherical equivalent progression (SEP) during the first year, subjects were subdivided into three groups: slow, moderate and fast (annual SEP > -0.50 D, -1.00 D < annual SEP ≤ -0.50 D, annual SEP ≤ -1.00 D, respectively). After 1 year of 0.01% atropine treatment, SEP was -0.37 ± 0.23 D, -0.57 ± 0.38 D, and -0.68 ± 0.49 D in the slow, moderate, and fast progression groups (P = 0.17). The group with faster SEP during the first year still showed faster SEP after treatment. The reduction of SEP (SEP of the second year minus SEP of the first year) in the moderate group was more than that in the slow group (0.22 ± 0.37 D vs. -0.10 ± 0.21 D, P = 0.007); the fast group was more than that in the slow group (0.57 ± 0.55 D vs. -0.10 ± 0.21 D, P < 0.001) and the moderate group (0.57 ± 0.55 D vs. 0.22 ± 0.37 D, P = 0.02). Faster SEP before treatment is related to the reduction efficiency (β = -0.5, P = 0.01). Faster SEP before treatment is associated with a better treatment response to 0.01% atropine eye drops, with greater reduction in SEP after treatment. However, no significant association was found between baseline progression and axial elongation changes. Children with slow SEP cannot get significant myopia control benefit from 1-year 0.01% atropine treatment. clinicaltrials.gov, identifier ChiCTR-IOR-17013898.

Comments on Diversified segmental defocus optimization lenses with and without atropine for myopia prevention: a randomized clinical trial.

Michaud Langis L

Unraveling the Molecular Origin of the Unprecedented ortho-Chloride Effect in Cobalt-Catalyzed Asymmetric Hydrogenation of 1,1-Diarylethenes.

Mahato Akhilesh A, Mahato Anupama A, Pramanik Anup A, Sarkar Pranab P

The molecular origin of the unusual ortho-chloride effect in cobalt-catalyzed asymmetric hydrogenation of 1,1-diarylethenes has been investigated using density functional theory. The complete catalytic cycle, including alkene coordination, alkene insertion, hydrogen activation, and catalyst regeneration, was elucidated on the relevant spin surfaces. The calculations identify alkene insertion into the Co-H bond via TS1 as the enantiodetermining step, whereas catalyst regeneration is the turnover-determining step. The preferred Si-face hydride transfer is favored by 3.79 kcal/mol, corresponding to a predicted 99.6% enantiomeric excess, in excellent agreement with the experimentally observed more than 90% ee. Activation strain, AIM, NCI, and NBO analyses reveal that reduced structural distortion together with enhanced noncovalent and donor-acceptor interactions stabilizes the transition state leading to the S enantiomer. Systematic investigation of substituent effects demonstrates that only the ortho-chloro substituent provides the optimal energetic balance, whereas meta- and para-substitution or replacement by other ortho substituents substantially diminishes enantioselectivity. These findings provide the first molecular-level explanation of the ortho-chloride effect and offer guiding principles for designing highly enantioselective cobalt catalysts.

Late-Diagnosed Cystic Fibrosis in an Octogenarian With an Atypical Phenotype of Pancreatic Sufficiency and Preserved Pulmonary Function.

Hranec Brenda B, Hudson Luke L, Layish Daniel D

Cystic fibrosis (CF) was historically described as a severe childhood disease associated with pancreatic destruction, malnutrition, recurrent respiratory infection, and early mortality. Advances in sweat chloride testing, cystic fibrosis transmembrane conductance regulator (CFTR) gene discovery, newborn screening, multidisciplinary care, and CFTR modulator therapy have transformed the natural history of the disease. However, CF remains clinically heterogeneous, and patients with residual CFTR function may present later in life with chronic bronchiectasis, sinus disease, atypical respiratory infections, or nonspecific gastrointestinal symptoms. Diagnosis in advanced age is uncommon and may be delayed when pancreatic function is preserved and sweat chloride values are intermediate. An 87-year-old woman with late-diagnosed cystic fibrosis was followed longitudinally for chronic sinopulmonary disease. She had a history of recurrent sinus infections and was evaluated at a tertiary institution, where CF was diagnosed at approximately age 62. Her family history was notable for a maternal aunt who died from an unspecified respiratory illness. Diagnostic evaluation demonstrated an intermediate sweat chloride value of 41 mmol/L and CFTR testing showing one copy of F508del, M470V polymorphism, and a rare C76W variant. Her phenotype included chronic bronchiectasis, chronic sinusitis with nasal polyps, two prior sinus surgeries, and prior Mycobacterium avium complex infection treated in 1995. She had pancreatic sufficiency, with normal fecal elastase and no clinical response to pancreatic enzyme replacement therapy. Pulmonary function testing showed preserved lung function with stage I obstruction, including FEV1 1.33 L, 89% predicted; FVC 1.95 L, 85% predicted; and FEV1/FVC ratio of 68%, stable compared with the prior year. Her course was also notable for osteoporosis with prior vertebral compression fractures, which limited tolerance of vest-based airway clearance. Management included airway clearance with an oscillatory positive expiratory pressure device, individualized bronchodilator therapy due to tachycardia with albuterol, surveillance respiratory cultures, nutritional and weight monitoring, otolaryngology follow-up for chronic sinusitis and nasal polyps, osteoporosis management, and treatment with vanzacaftor/tezacaftor/deutivacaftor, to which she reported symptomatic improvement. This case highlights an uncommon late-diagnosed CF phenotype in an octogenarian with pancreatic sufficiency, intermediate sweat chloride, chronic sinopulmonary disease, preserved lung function, and new isolation of Pseudomonas aeruginosa. The case emphasizes that preserved pancreatic function and advanced age do not exclude CF and that adult patients with chronic bronchiectasis, sinus disease, and atypical respiratory infections should be evaluated for CFTR dysfunction when clinically appropriate.