Reproductive characteristics, use of exogenous hormones and Parkinson disease in women from the E3N study.

Despite experimental studies suggesting a disease-modifying role of oestrogens, results from epidemiological studies on the relation of reproductive characteristics and hormonal exposures with Parkinson disease in women are conflicting. We used the data from the E3N cohort study including 98 068 women aged 40-65 years in 1990 followed until 2018. Parkinson disease was ascertained using a validation process based on drug claim databases and medical records. Reproductive characteristics and hormonal exposures were self-reported (11 questionnaires). Associations of exposures with Parkinson disease incidence were investigated using time-varying Cox proportional hazards regression with a 5-year exposure lag and age as the timescale adjusted for confounders. We identified 1165 incident Parkinson disease cases during a mean follow-up of 22.0 years (incidence rate = 54.7 per 100 000 person-years). Parkinson disease incidence was higher in women with early (<12 years, HR = 1.21, 95% CI = 1.04-1.40) or late age at menarche (≥14 years, HR = 1.18, 95% CI = 1.03-1.35) than in women with menarche at 12-13 years. Nulliparity was not associated with Parkinson disease, but Parkinson disease incidence increased with the number of children in parous women (P-trend = 0.009). Women with artificial (surgical, iatrogenic) menopause were at greater risk than women with natural menopause (HR = 1.28, 95% CI = 1.09-1.47), especially when artificial menopause occurred at an early age (≤45.0 years). Postmenopausal hormone therapy tended to mitigate greater risk associated with artificial or early menopause (≤45.0 years). While fertility treatments were not associated with Parkinson disease overall, ever users of clomiphene were at greater Parkinson disease risk than never users (HR = 1.81, 95% CI = 1.14-2.88). Other exposures (breastfeeding, oral contraceptives) were not associated with Parkinson disease. Our findings suggest that early and late age at menarche, higher parity, and artificial menopause, in particular at an early age, are associated with increased Parkinson disease incidence in women. In addition, there was some evidence that use of exogenous hormones may increase (fertility treatments) or decrease (postmenopausal hormone therapy) Parkinson disease incidence. These findings support the hypothesis that hormonal exposures play a role in the susceptibility to neurodegenerative diseases. If confirmed, they could help to identify subgroups at high risk for Parkinson disease.

Developmental transcriptomes predict adult social behaviours in the socially flexible sweat bee, Lasioglossum baleicum.

Natural variation can provide important insights into the genetic and environmental factors that shape social behaviour and its evolution. The sweat bee, Lasioglossum baleicum, is a socially flexible bee capable of producing both solitary and eusocial nests. We demonstrate that within a single nesting aggregation, soil temperatures are a strong predictor of the social structure of nests. Sites with warmer temperatures in the spring have a higher frequency of social nests than cooler sites, perhaps because warmer temperatures provide a longer reproductive window for those nests. To identify the molecular correlates of this behavioural variation, we generated a de novo genome assembly for L. baleicum, and we used transcriptomic profiling to compare adults and developing offspring from eusocial and solitary nests. We find that adult, reproductive females have similar expression profiles regardless of social structure in the nest, but that there are strong differences between reproductive females and workers from social nests. We also find substantial differences in the transcriptomic profiles of stage-matched pupae from warmer, social-biased sites compared to cooler, solitary-biased sites. These transcriptional differences are strongly predictive of adult reproductive state, suggesting that the developmental environment may set the stage for adult behaviours in L. baleicum. Together, our results help to characterize the molecular mechanisms shaping variation in social behaviour and highlight a potential role of environmental tuning during development as a factor shaping adult behaviour and physiology in this socially flexible bee.

Statin Use and Incidence of Parkinson's Disease in Women from the French E3N Cohort Study.

BACKGROUND: Statins represent candidates for drug repurposing in Parkinson's disease (PD). Few studies examined the role of reverse causation, statin subgroups, and dose-response relations based on time-varying exposures. OBJECTIVES: We examined whether statin use is associated with PD incidence while attempting to overcome the limitations described previously, especially reverse causation. METHOD: We used data from the E3N cohort study of French women (follow-up, 2004-2018). Incident PD was ascertained using multiple sources and validated by experts. New statin users were identified through linked drug claims. We set up a nested case-control study to describe trajectories of statin prescriptions and medical consultations before diagnosis. We used time-varying multivariable Cox proportional hazards regression models to examine the statins-PD association. Exposure indexes included ever use, cumulative duration/dose, and mean daily dose and were lagged by 5 years to address reverse causation. RESULTS: The case-control study (693 cases, 13,784 controls) showed differences in case-control trajectories, with changes in the 5 years before diagnosis in cases. Of 73,925 women (aged 54-79 years), 524 developed PD and 11,552 started using statins in lagged analyses. Ever use of any statin was not associated with PD (hazard ratio [HR] = 0.87, 95% confidence interval [CI] = 0.67-1.11). Alternatively, ever use of lipophilic statins was significantly associated with lower PD incidence (HR = 0.70, 95% CI = 0.51-0.98), with a dose-response relation for the mean daily dose (P-linear trend = 0.02). There was no association for hydrophilic statins. CONCLUSION: Use of lipophilic statins at least 5 years earlier was associated with reduced PD incidence in women, with a dose-response relation for the mean daily dose. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Group size rather than social status influences personal immune efficacy in a socially polymorphic bee.

The evolution of group living is associated with increased pressure from parasites and pathogens. This can be offset by greater investment in personal immune defences and/or the development of cooperative immune defences (social immunity). An enduring question in evolutionary biology is whether social-immune benefits arose in response to an increased need in more complex societies, or arose early in group living and helped facilitate the evolution of more complex societies. In this study, we shed light on this question through investigating how immunity varies intraspecifically in a socially polymorphic bee. Using a novel immune assay, we show that personal antibacterial efficacy in individuals from social nests is higher than that of solitary individuals, but that this can be explained by higher densities in social nests. We conclude that personal immune effects are likely to play a role in the social/solitary transition in this species. These patterns are consistent with the idea that social immunity evolved secondarily, following the evolution of group living. The flexibility of the individual immune system may have favoured a reliance on its use during the facultative phase early in social evolution.

Identifying Protective Drugs for Parkinson's Disease in Health-Care Databases Using Machine Learning.

BACKGROUND: Available treatments for Parkinson's disease (PD) are only partially or transiently effective. Identifying existing molecules that may present a therapeutic or preventive benefit for PD (drug repositioning) is thus of utmost interest. OBJECTIVE: We aimed at detecting potentially protective associations between marketed drugs and PD through a large-scale automated screening strategy. METHODS: We implemented a machine learning (ML) algorithm combining subsampling and lasso logistic regression in a case-control study nested in the French national health data system. Our study population comprised 40,760 incident PD patients identified by a validated algorithm during 2016 to 2018 and 176,395 controls of similar age, sex, and region of residence, all followed since 2006. Drug exposure was defined at the chemical subgroup level, then at the substance level of the Anatomical Therapeutic Chemical (ATC) classification considering the frequency of prescriptions over a 2-year period starting 10 years before the index date to limit reverse causation bias. Sensitivity analyses were conducted using a more specific definition of PD status. RESULTS: Six drug subgroups were detected by our algorithm among the 374 screened. Sulfonamide diuretics (ATC-C03CA), in particular furosemide (C03CA01), showed the most robust signal. Other signals included adrenergics in combination with anticholinergics (R03AL) and insulins and analogues (A10AD). CONCLUSIONS: We identified several signals that deserve to be confirmed in large studies with appropriate consideration of the potential for reverse causation. Our results illustrate the value of ML-based signal detection algorithms for identifying drugs inversely associated with PD risk in health-care databases. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Incidence of Parkinson's disease in French women from the E3N cohort study over 27 years of follow-up.

Parkinson's disease (PD) is an uncommon disease with a long prodromal period and higher incidence in men than women. Large cohort studies of women with a long follow-up are needed. Within the E3N French cohort study (98,995 women, 40-65 years at baseline), we identified 3,584 participants who self-reported PD or used anti-parkinsonian drugs over 27 years (1992-2018). We obtained medical records to validate PD diagnosis (definite, probable, possible, no). When medical records were not available, we used a validated algorithm based on drug claims to predict PD status. We retained a PD diagnosis for 1,294 women (medical records, 62%; algorithm, 38%). After exclusion of prevalent/possible cases, cases without age at diagnosis, and women lost to follow-up, our analyses included 98,069 women, of whom 1,200 had incident PD (mean age at diagnosis = 71.8 years; incidence rate = 0.494/1,000 person-years). Age-adjusted incidence rates increased over the six first years of follow-up, possibly due to healthy volunteer bias, and remained stable thereafter, similar to incidence rates in women from Western Europe. Forty three percent of PD cases occurred after 20 years of follow-up (2012-2018). The cumulative incidence of PD from 50 to 90 years was 2.41% (95% confidence interval [CI] = 2.27-2.65). PD incidence was lower in ever than never smokers (hazard ratio = 0.86, 95% CI = 0.76-0.96). In conclusion, we estimated PD incidence rates in French women over a 27-year follow-up, and showed stable incidence between 2002 and 2018. The long follow-up and large sample size make this study a valuable resource to improve our knowledge on PD etiology in women.

Natural Prenylated Xanthones as Potential Inhibitors of PI3k/Akt/mTOR Pathway in Triple Negative Breast Cancer Cells.

Three prenylated xanthones, garcinone E (1: ), bannaxanthone D (2: ) and bannanxanthone E (3: ) were isolated from the leaves of Garcinia mckeaniana Graib. Their structures were elucidated by spectral methods and compared with literature data. To evaluate their anti-proliferative effects in tumor cells, firstly, cisplatin was used as a positive control and the effects of compound 1:  - 3: were determined by performing MTT assay in MDA-MB-231, CNE-2 and A549 cancer cells. The results showed compound 1:  - 3: exhibited stronger inhibitory effect than cisplatin in MDA-MB-231. Further effects of compound 1:  - 3: in TNBC MDA-MB-231 and MDA-MB-468 cells were examined by performing cell cycle and apoptosis assays. The results indicated that compound 1:  - 3: had ability to arrest cell cycle at G2/M phase and induce apoptosis. Furthermore, compound 2: significantly down-regulated PI3K, Akt and mTOR levels in both total proteins and phosphorylated form, which is its potential anti-cancer mechanism. These findings indicated that those prenylated xanthones might serve as promising leading compounds for the development of anticancer drug for TNBC.

A Novel Synthetic Antibody Library with Complementarity-Determining Region Diversities Designed for an Improved Amplification Profile.

Antibody discovery by phage display consists of two phases, i.e., the binding phase and the amplification phase. Ideally, the selection process is dominated by the former, and all the retrieved clones are amplified equally during the latter. In reality, the amplification efficiency of antibody fragments varies widely among different sequences and, after a few rounds of phage display panning, the output repertoire often includes rapidly amplified sequences with low or no binding activity, significantly diminishing the efficiency of antibody isolation. In this work, a novel synthetic single-chain variable fragment (scFv) library with complementarity-determining region (CDR) diversities aimed at improved amplification efficiency was designed and constructed. A previously reported synthetic scFv library with low, non-combinatorial CDR diversities was panned against protein A superantigen, and the library repertoires before and after the panning were analyzed by next generation sequencing. The enrichment or depletion patterns of CDR sequences after panning served as the basis for the design of the new library. Especially for CDR-H3 with a higher and more random diversity, a machine learning method was applied to predict potential fast-amplified sequences among a simulated sequence repertoire. In a direct comparison with the previous generation library, the new library performed better against a panel of antigens in terms of the number of binders isolated, the number of unique sequences, and/or the speed of binder enrichment. Our results suggest that the amplification-centric design of sequence diversity is a valid strategy for the construction of highly functional phage display antibody libraries.

Synthesis and biological evaluation of novel benzo[a]pyridazino[3,4-c]phenazine derivatives.

A convenient microwave-assisted one-pot four-component synthetic approach was developed en route to novel functionalized benzo[a]pyridazino[3,4-c]phenazine derivatives starting from 2-hydroxy-1,4-naphthoquinone, aromatic aldehydes, methyl hydrazine and o-phenylenediamine. Nine new derivatives were successfully synthesized and subsequently evaluated in terms of their biological profiles. The results revealed good cytotoxic activities of compounds 6a, 6h against KB, HepG2, Lu1 and MCF7 human cancer cell lines. Besides that, compound 6d exhibited promising antimicrobial activities toward Staphylococcuc aureus and Bacillus subtilis bacterial strains with IC50 < 6 µM.

Synthesis of novel potent cytotoxicy podophyllotoxin-naphthoquinone compounds via microwave-assited multicomponent domino reactions.

A series of novel podophyllotoxin-naphthoquinone compounds 5a-p were synthesized in good yields using microwave-assisted four-component reactions of 2-hydroxy-1,4-naphthoquinone, aromatic benzaldehydes, tetronic acid and ammonium acetate. All the synthesized compounds were fully characterized by spectral data and evaluated for their cytotoxicity activities against KB, HepG2, Lu1, MCF7, and non-cancerous Hek-293 cell lines. Among 16 new compounds screened, compounds 5a, 5d, 5h, and 5k displayed high potent inhibitory activities with IC50 < 40 nM against HepG2 and SK-Lu-1 cell lines, and showed lower toxicity for non-cancerous Hek-293 cell line, demonstrating the potential importance of these compounds in the development of potential anticancer agents.

Complexation of Cyclodextrins with Benzoic Acid in Water-Organic Solvents: A Solvation-Thermodynamic Approach.

The aim of this research is to obtain new data about the complexation between ß-cyclodextrin (ß-CD) and benzoic acid (BA) as a model reaction of the complex formation of hydrophobic molecules with cyclodextrins (CDs) in various media. This research may help developing cyclodextrin-based pharmaceutical formulations through the choice of the appropriate solvent mixture that may be employed in the industrial application aiming to control the reactions/processes in liquid phase. In this paper, NMR results for the molecular complex formation between BA and ß-CD ([BA⊂ß-CD]) in D2O-DMSO-d6 and in D2O-EtOH have shown that the stability of the complex in the H2O-DMSO-d6 varies within the experimental error, while decreases in H2O-EtOH. Changes in the Gibbs energy of BA resolvation in water and water-dimethylsulfoxide mixtures have been obtained and have been used in the analysis of the reagent solvation contributions into the Gibbs energy changes of the [BA⊂ß-CD] molecular complex formation. Quantum chemical calculations of the interaction energy between ß-CD and BA as well as the structure of the [BA⊂ß-CD] complex and the energy of ß-CD and BA interaction in vacuum and in the medium of water, methanol and dimethylsulfoxide solvents are carried out. The stability of [BA⊂ß-CD] complex in H2O-EtOH and H2O-DMSO solvents, obtained by different methods, are compared. The thermodynamic parameters of the [BA⊂ß-CD] molecular complexation as well as the reagent solvation contributions in H2O-EtOH and H2O-DMSO mixtures were analyzed by the solvation-thermodynamic approach.

Synthesis and biological evaluation of novel quinazoline-triazole hybrid compounds with potential use in Alzheimer's disease.

A library of twelve quinazoline-triazole hybrid compounds were designed, synthesized and evaluated as a novel class of acetylcholinesterase inhibitors to treat Alzheimer's disease (AD). The biological assay results demonstrated the ability of several hybrid compounds to inhibit AChE enzyme (IC50 range = 0.2-83.9 µM). To understand the high potential activity of these compounds, molecular docking simulations were performed to get better insights into the mechanism of binding of quinazoline-triazole hybrid compounds. As expected, compounds 8a and 9a-b bind to both catalytic anionic site (CAS) and peripheral anionic site (PAS) in the active site of AChE enzyme, which implicates that these compounds could act as dual binding site inhibitors. These compounds were not cytotoxic and they also displayed appropriated physicochemical as well as pharmacokinetic profile to be developed as novel anti-AD drug candidates.

Antidepressants and movement disorders: a postmarketing study in the world pharmacovigilance database.

BACKGROUND: Antidepressants-induced movement disorders are rare and imperfectly known adverse drug reactions. The risk may differ between different antidepressants and antidepressants' classes. The objective of this study was to assess the putative association of each antidepressant and antidepressants' classes with movement disorders. METHODS: Using VigiBase®, the WHO Pharmacovigilance database, disproportionality of movement disorders' reporting was assessed among adverse drug reactions related to any antidepressant, from January 1967 to February 2017, through a case/non-case design. The association between nine subtypes of movement disorders (akathisia, bruxism, dystonia, myoclonus, parkinsonism, restless legs syndrome, tardive dyskinesia, tics, tremor) and antidepressants was estimated through the calculation first of crude Reporting Odds Ratio (ROR), then adjusted ROR on four potential confounding factors: age, sex, drugs described as able to induce movement disorders, and drugs used to treat movement disorders. RESULTS: Out of the 14,270,446 reports included in VigiBase®, 1,027,405 (7.2%) contained at least one antidepressant, among whom 29,253 (2.8%) reported movement disorders. The female/male sex ratio was 2.15 and the mean age 50.9 ± 18.0 years. We found a significant increased ROR for antidepressants in general for all subtypes of movement disorders, with the highest association with bruxism (ROR 10.37, 95% CI 9.62-11.17) and the lowest with tics (ROR 1.49, 95% CI 1.38-1.60). When comparing each of the classes of antidepressants with the others, a significant association was observed for all subtypes of movement disorders except restless legs syndrome with serotonin reuptake inhibitors (SRIs) only. Among antidepressants, mirtazapine, vortioxetine, amoxapine, phenelzine, tryptophan and fluvoxamine were associated with the highest level to movement disorders and citalopram, paroxetine, duloxetine and mirtazapine were the most frequently associated with movement disorders. An association was also found with eight other antidepressants. CONCLUSIONS: A potential harmful association was found between movement disorders and use of the antidepressants mirtazapine, vortioxetine, amoxapine, phenelzine, tryptophan, fluvoxamine, citalopram, paroxetine, duloxetine, bupropion, clomipramine, escitalopram, fluoxetine, mianserin, sertraline, venlafaxine and vilazodone. Clinicians should beware of these adverse effects and monitor early warning signs carefully. However, this observational study must be interpreted as an exploratory analysis, and these results should be refined by future epidemiological studies.

An original pharmacoepidemiological-pharmacodynamic method: application to antipsychotic-induced movement disorders.

AIMS: Pharmacovigilance databases are usually used to detect new potential signals that are relevant for drug safety. They are seldom used for explanatory purposes, e.g. to understand the mechanisms of adverse drug reactions (ADRs). The aim of the present study was to combine pharmacovigilance and pharmacodynamic data to investigate the association between dopamine D2, serotonin 5HT2A, and muscarinic M1 receptor occupancy and the risks of antipsychotic drug (AP)-induced movement disorders. METHODS: First, we performed a case-noncase analysis using spontaneous reports from the World Health Organization (WHO) Global Individual Case Safety Report (ICSR) database, VigiBase®. We thus measured the risk of reporting movement disorders compared with all other ADRs [expressed as a reporting odds ratio (ROR)] for APs. Second, we performed a linear regression analysis to explore the association between the estimated risk of reporting for individual drugs and their receptor occupancy properties, for D2, 5HT2A and M1 receptors. RESULTS: Compared with second-generation APs, first-generation APs were found to be significantly more associated with the reporting of movement disorders in general but also with dystonia, Parkinsonism, akathisia and tardive dyskinesia, irrespective of gender. A significant inverse correlation was found between the ROR for movement disorders and the receptor occupancy of 5HT2A [P < 0.001; R2  = 0.51; slope = -0.014; 95% confidence interval (CI) (-0.029, 0.001)], M1 (P < 0.001; R2  = 0.56; slope = -0.014; 95% CI (-0.028, 0.001) but not D2 dopamine (P = 0.54; R2  = 0.02; slope = -0.003; 95% CI (-0.007, 0.001) receptors. CONCLUSIONS: Using the example of AP-induced movement disorders, the present study underlines the value of the pharmacoepidemiological-pharmacodynamic method to explore ADR mechanisms in humans and real-life settings.

Computational assay of Zanamivir binding affinity with original and mutant influenza neuraminidase 9 using molecular docking.

Based upon molecular docking, this study aimed to find notable in silico neuraminidase 9 (NA9) point mutations of the avian influenza A H7N9 virus that possess a Zanamivir resistant property and to determine the lead compound capable of inhibiting these NA9 mutations. Seven amino acids (key residues) at the binding site of neuraminidase 9 responsible for Zanamivir-NA9 direct interactions were identified and 72 commonly occurring mutant NA9 versions were created using the Sybyl-X 2.0 software. The docking scores obtained after Zanamivir was bound to all mutant molecules of NA9 revealed 3 notable mutations R292W, R118P, and R292K that could greatly reduce the binding affinity of the medicine. These 3 mutant NA9 versions were then bound to each of 154 different molecules chosen from 5 groups of compounds to determine which molecule(s) might be capable of inhibiting mutant neuraminidase 9, leading to the discovery of the lead compound of potent mutant NA9 inhibitors. This compound, together with other mutations occurring to NA9 identified in the study, would be used as data for further research regarding neuraminidase inhibitors and synthesizing new viable medications used in the fight against the virus.

Computational, optical and feasibility studies of organic luminescence TMB-PPT blend for photovoltaic application.

For enhanced applications of solar cells, organic luminescence materials like long persistent luminescence (LPL) present one of the promising avenues for light enhancement. Currently, most existing luminescent materials are based on an inorganic system that requires rare elements such as europium and dysprosium, with a very high processing temperature. Adopting organic luminescence materials that are free from rare elements is necessary, considering the low-temperature fabrication and low material cost. In this work, we investigate the optical properties of an organic luminescence blend consisting of 2,8-bis(diphenylphosphoryl)dibenzo [b,d]thiophene (PPT) and N,N,N',N'-tetramethylbenzidine (TMB) through computational studies and experimental validations. Optical characteristics of the luminescence materials like optical absorption, photoluminescence, and time-resolved photoluminescence spectroscopy are characterized. To validate the functionality of the organic luminescence blend, the material is incorporated into the perovskite solar cell structure. Unfortunately, the blend is unable to emit sufficient illumination over extended periods due to its low intersystem crossing efficiency and weak spin-orbit coupling. Although the power conversion efficiency of the Luminescence/FTO/TiO2/Perovskite/Carbon structure is observed to be small under dark conditions, the application of organic luminescence materials can be further enhanced and explored.

High Ferritin and Low Total Iron-Binding Capacity in Plasma Predict All-Cause Mortality During the First 3 Years of Hemodialysis in Patients with End-Stage Chronic Kidney Disease.

Aim: To determine all-cause mortality rate and the predictive value of plasma ferritin and total iron-binding capacity (TIBC) concentrations for mortality during the first 3 years of hemodialysis in patients with end-stage chronic renal disease (ESRD). Methods: We conducted a study on 174 ESRD patients (estimated Glomerular Filtration Rate < 15 mL/min/1.73m2). The plasma TIBC level was quantified by the ELISA method in all patients at the time before hemodialysis. Based on TIBC concentration, patients were divided equally into 2 groups. Each group had 87 patients. Patients were initiated on hemodialysis, and patients who died from any cause during the first 3 years of hemodialysis were recorded. Results: The all-cause mortality rate of ESRD patients in the first 3 years of maintenance hemodialysis was 22.9%. Plasma high hs-CRP, high ferritin, and low TIBC concentrations were independent factors associated with all-cause mortality in the patients. Plasma ferritin (cut-off value = 454.2 ng/L) and TIBC (cut-off value = 39.84 µmol/L) were predictors of all-cause mortality, AUC is: 0.772; 0.723, p < 0.001. Conclusion: Plasma ferritin and TIBC were good predictors of all-cause mortality in ESRD patients during the first 3 years of hemodialysis.

Assessment of the Effectiveness of Ultrasound-Guided Needle Aspiration of Lactating Breast Abscesses.

Objective: To evaluate the effectiveness of ultrasound-guided needle aspiration in treating lactating breast abscesses. Methods: This study was conducted in Bach Mai Hospital, from 6/2020 to 7/2021. Lactating patients with breast abscesses underwent ultrasound-guided aspiration followed by antibiotics therapy. Results: There were 59 lactating patients with 82 breast abscesses. Most of the abscesses had heterogeneous echogenicity, no capsule, and a size smaller than 5cm. Bacterial culture results showed that 85.4% of cases were Methicillin-resistant Staphylococcus aureus. The number of aspirations was from 1 to 5. The cure rate was 91.5%, and 5.3% of these cases had a complication associated with galactocele after treatment. Conclusion: Ultrasound-guided needle aspiration is a minimally invasive treatment option for lactating breast abscesses with a high complete cure rate and good cosmetic results.

Dry Eye and Some Related Factors in Patients with Type 2 Diabetic Nephropathy: A Cross-Sectional Study in Vietnam.

Aim: To determine the prevalence of dry eye (DE) and some related factors in patients with type 2 diabetic nephropathy (T2DN). Methods: We performed a cross-sectional study on 338 people, who were divided into 2 groups: 169 T2DN patients and 169 patients diagnosed with type 2 diabetic mellitus (T2DM) without renal complications as a control group. The Ocular Surface Disease Index (OSDI) and test fluorescein tear-film break-up time (TBUT) were done in all 338 subjects. Patients with OSDI scores < 13 and TBUT values equal to or under 10 seconds were diagnosed with dry eye. Results: The prevalence of DE in T2DN patients was significantly higher than T2DM group (55.6% versus 37.3%). The T2DN groups with dry eye had a median duration of DM, the proportion of hypertension, peripheral nerve complications, anemia, proportion of using insulin, and concentration of plasma glucose, HbA1C, urea, creatinine, CRP-hs significantly higher than those of T2DN without dry eye. Advanced age, high HbA1C level, and decreased eGFR were independent factors associated with dry eye in T2DN patients. Conclusion: Dry eye was a common condition associated with advanced age, high HbA1C levels, and decreased GFR in T2DN patients.

Construction of Rabbit Immune Antibody Libraries.

Rabbits have distinct advantages over mice as a source of target-specific antibodies. They produce higher affinity antibodies than mice and may elicit strong immune response against antigens or epitopes that are poorly immunogenic or tolerated in mice. However, a great majority of currently available monoclonal antibodies are of murine origin because of the wider availability of murine fusion partner cell lines and well-established tools and protocols for fusion and cloning of mouse hybridoma. Phage display selection of antibody libraries is an alternative method to hybridoma technology for the generation of target-specific monoclonal antibodies. High-affinity monoclonal antibodies from non-murine species can readily be obtained by constructing immune antibody libraries from B cells of the immunized animal and screening the library by phage display. In this article, we describe the construction of a rabbit immune Fab library for the facile isolation of rabbit monoclonal antibodies. After immunization, B-cell cDNA is obtained from the spleen of the animal, from which antibody variable domain repertoires are amplified and assembled into a Fab repertoire by PCR. The Fab genes are then cloned into a phagemid vector and transformed to E. coli, from which a phage-displayed immune Fab library is rescued. Such a library can be biopanned against the immunization antigen for rapid identification of high-affinity, target-specific rabbit monoclonal antibodies.