Genotype-phenotype profile of global ASPH-associated ectopia lentis and clinical findings from a Chinese cohort.

BACKGROUND: Traboulsi syndrome is an under-recognized syndromic form of ectopia lentis (EL) caused by the aspartate beta-Hydroxylase (ASPH) variant. The genotype-phenotype profile of ASPH-associated disease is poorly understood due to the rarity of the condition. METHODS: We conducted targeted next-generation sequencing and bioinformatics analysis to identify potentially pathogenic ASPH variants in the cohort. Furthermore, we characterized the expression pattern of ASPH and major components of the zonules using single-cell RNA-sequencing (scRNA-seq) and evaluated the genotype-phenotype correlations by combining our data and those from the literature. RESULTS: We identified a novel missense variant c.2075G > A (p.G692D) and a recurrent nonsense variant c.1126C > G (p.R376*) of ASPH in two pedigrees from a Chinese cohort of EL. Both probands were 5-year-old boys with canonical facial dysmorphisms and bilateral anteriorly-dislocated lenses. Other ocular comorbidities included microspherophakia, shallow anterior chamber, and narrow chamber angel. No cardiac involvements or filtering blebs were identified. The single-cell expression atlas of ciliary epithelium demonstrated the coexpression of ASPH with FBN1, FBN2, and LTBP2 in the non-pigmented ciliary epithelium cells. Furthermore, molecular modeling simulation of p.G692D revealed increased affinity to the cb EGF-like domain and a subsequent destabilized calcium-binding motif. The genotype-phenotype analysis demonstrated that patients with cardiac involvements all harbored biallelic truncation variants. CONCLUSIONS: The data from this study provide new insights into the genotype-phenotype profile of ASPH-associated disease and implicate the potential role of ASPH in the pathogenesis of EL.

Dual "on-off" signal conversion strategy based on surface plasmon coupling and resonance energy transfer for visual electrochemiluminescence ratiometric analysis of MiRNA-141.

An electrochemiluminescence (ECL) biosensor with a pair of new ECL emitters and a novel sensing mechanism was designed for the high-sensitivity detection of microRNA-141 (miRNA-141). Sulfur-doped boron nitrogen quantum dots (S-BN QDs) were initially employed to modify the cathode of the bipolar electrode (BPE), while the anode reservoir was [Ir(dfppy)2(bpy)]PF6/TPrA system. The next step involved attaching H1-bound ultra-small WO3-x nanodots (WO3-x NDs) to the S-BN QDs-modified BPE cathode via DNA hybridization. A strong surface plasmon coupling (SPC) effect was observed between S-BN QDs and WO3-x NDs, which allowed for the enhancement of the red and visible ECL emission from S-BN QDs. After target-induced cyclic amplification to produce abundant Zn2+ and Au NPs-DNA3-Au NPs (Au NPs-S3-Au NPs), Zn2+ could cleave DNA at a nucleotide sequence-specific recognition site to release the WO3-x NDs, resulting in the first diminution of cathode ECL signal and the first enhancement of anode ECL signal. Moreover, the ECL signal at cathode decreased for the second time and the emission of [Ir(dfppy)2(bpy)]PF6 was continuously enhanced after the introduction of Au nanoparticles-S3-Au nanoparticles on the cathode surface. Our sensing mode with a dual "on-off" signal conversion strategy shows a good detection capability for miRNAs ranging from 10-17 to 10-10 M, with a limit of detection (LOD) as low as 10-17 M, which has great application potential in biomedical research and clinical diagnosis.

Template Synthesis to Solve the Unreachable Ortho C-H Functionalization Reaction of Aryl Iodide.

This report describes the use of a simple Pd/NBE catalytic system to achieve ortho C-H oxylation and phosphonylation and other functionalizations of aryl iodide through templated conversion reactions. Dimethylamine is introduced in the ortho-site of aryl iodide through C-H amination, and aryl dimethylamine is quickly converted to methyl quaternary ammonium salt precipitation. Methyl quaternary ammonium salt avoids Hofmann elimination in subsequent functionalization. This method solves various ortho functionalization reactions of aryl iodide that have not been achieved for a long time in the field of Pd/NBE chemistry indirectly.

Development of a clinical automatic calculation of hypoglycemia during hemodialysis risk in patients with diabetic nephropathy.

BACKGROUND: Hypoglycemia is one of the most common complications in patients with DN during hemodialysis. The purpose of the study is to construct a clinical automatic calculation to predict risk of hypoglycemia during hemodialysis for patients with diabetic nephropathy. METHODS: In this cross-sectional study, patients provided information for the questionnaire and received blood glucose tests during hemodialysis. The data were analyzed with logistic regression and then an automated calculator for risk prediction was constructed based on the results. From May to November 2022, 207 hemodialysis patients with diabetes nephropathy were recruited. Patients were recruited at blood purifying facilities at two hospitals in Beijing and Inner Mongolia province, China. Hypoglycemia is defined according to the standards of medical care in diabetes issued by ADA (2021). The blood glucose meter was used uniformly for blood glucose tests 15 minutes before the end of hemodialysis or when the patient did not feel well during hemodialysis. RESULTS: The incidence of hypoglycemia during hemodialysis was 50.2% (104/207). The risk prediction model included 6 predictors, and was constructed as follows: Logit (P) = 1.505×hemodialysis duration 8~15 years (OR = 4.506, 3 points) + 1.616×hemodialysis duration 16~21 years (OR = 5.032, 3 points) + 1.504×having hypotension during last hemodialysis (OR = 4.501, 3 points) + 0.788×having hyperglycemia during the latest hemodialysis night (OR = 2.199, 2 points) + 0.91×disturbance of potassium metabolism (OR = 2.484, 2 points) + 2.636×serum albumin<35 g/L (OR = 13.963, 5 points)-4.314. The AUC of the prediction model was 0.866, with Matthews correlation coefficient (MCC) of 0.633, and Hosmer-Lemeshow χ2 of 4.447(P = 0.815). The automatic calculation has a total of 18 points and four risk levels. CONCLUSIONS: The incidence of hypoglycemia during hemodialysis is high in patients with DN. The risk prediction model in this study had a good prediction outcome. The hypoglycemia prediction automatic calculation that was developed using this model can be used to predict the risk of hypoglycemia in DN patients during hemodialysis and also help identify those with a high risk of hypoglycemia during hemodialysis.

Changes of retinal vessel density in low to moderate myopic eyes with orthokeratology evaluated by optical coherence tomography angiography.

AIM: To explore the effect of orthokeratology (OK) fitting on retinal vessel density in low to moderate myopia adolescents by using optical coherence tomography angiography. METHODS: Children aged 10 to 14y with a cycloplegic spherical equivalent refraction of -0.50 diopter (D) to -5.00 D and astigmatism with more than -1.50 D were recruited. The enrolled adolescents were divided into OK group and spectacle group. During regular follow-up, adolescents were measured respectively at pre-wear, 1, 3, and 6mo after treatment. The follow-up included uncorrected distance visual acuity (UDVA), axial length (AL), superficial capillary plexus density (SCPD), deep capillary plexus density (DCPD), central retinal thickness (CRT), foveal avascular zone area (FAZ-A), foveal avascular zone perimeter (FAZ-P) and foveal vessel density in a 300-µm-wide region around foveal avascular zone (FD-300). The collected data were analyzed using statistical methods. RESULTS: By one month, SCPD significantly increased in the fovea and superior retina, and DCPD significantly increased inferiorly in OK group compared to spectacle group (P<0.05). By three months, there were significant increases in SCPD in the fovea and inferior retina, and DCPD in the parafovea, superior, and inferior retina in OK group (P<0.05), while the increase in SCPD and DCPD in the fovea were observed by six months (P<0.05). The FD-300 significantly increased at every follow-up in OK group compared to spectacle group (P<0.05). No significant differences in the CRT, FAZ-A and FAZ-P and FD-300 were observed between two groups (P>0.05). OK group showed a significant improvement in UDVA after wearing OK, compared to spectacle group (P<0.01), while the AL did not show a significant difference between two groups (P>0.05). CONCLUSION: Short-term OK worn can increase local retinal vessel density in adolescents with low-to-moderate myopia.

Infection of sheep by Echinococcus multilocularis in Gansu, China: evidence from mitochondrial and nuclear DNA analysis.

BACKGROUND: In the normal life cycle of the parasite (Echinococcus multilocularis) that causes alveolar echinococcosis, domestic and wild carnivores act as definitive hosts, and rodents act as intermediate hosts. The presented study contributes to the research on the distribution and transmission pattern of E. multilocularis in China having identified sheep as an unusual intermediate host taking part in the domestic transmission of alveolar echinococcosis in Gansu Province, China. METHODS: From 2020 to 2021, nine whitish different cyst-like were collected from the liver of sheep in Gansu Province for examination. A near complete mitochondrial (mt) genome and selected nuclear genes were amplified from the cyst-like lesion for identification. To confirm the status of the specimen, comparative analysis with reference sequences, phylogenetic analysis, and network analysis were performed. RESULTS: The isolates displayed ≥ 98.87% similarity to E. multilocularis NADH dehydrogenase sub-unit 1 (nad1) (894 bp) reference sequences deposited in GenBank. Furthermore, amplification of the nad4 and nad2 genes also confirmed all nine samples as E. multilocularis with > 99.30% similarity. Additionally, three nuclear genes, pepck (1545 bp), elp-exons VII and VIII (566 bp), and elp-exon IX (256 bp), were successfully amplified and sequenced for one of the isolates with 98.42% similarity, confirming the isolates were correctly identified as E. multilocularis. Network analysis also correctly placed the isolates with other E. multilocularis. CONCLUSIONS: As a result of the discovery of E. multilocularis in an unusual intermediate host, which is considered to have the highest zoonotic potential, the result clearly demonstrated the necessity for expanded surveillance in the area.

Revealing novel cytb and nad5 genes-based population diversity and benzimidazole resistance in Echinococcus granulosus of bovine origin.

Cystic echinococcosis (CE) is a neglected zoonotic disease caused by Echinococcus granulosus (sensu stricto). The parasite affects a wide range of livestock and wild animals. In this study, the population diversity of the Echinococcus species was investigated based on mitochondrial cytochrome b (cytb) and NADH dehydrogenase subunit 5 (nad5) genes. In addition to this, ß-tubulin gene isoforms of Echinococcus granulosus were amplified to determine the resistance against benzimidazoles. For this purpose, 40 cyst samples from cattle (n = 20) and buffaloes (n = 20) were collected from the main abattoir of Sialkot. DNA extraction was performed using Qiagen Blood and Tissue Kits. Amplification was performed through PCR. Each amplicon was confirmed by GelRed™ stained agarose gel (2%). Samples were sequenced in a DNA analyzer and viewed for any misread nucleotide by using MEGA (v.11). Corrections in nucleotide sequence and multiple sequence alignment were made through the same software. NCBI-BLAST was used for sample specific sequences to identify them as belonging to a particular species. Diversity indices were estimated using DnaSP (v.6) while phylogenetic analysis was inferred using the Bayesian method using MrBayes (v.1.1). ß-tubulin gene isoforms sequence analysis was performed to find out the candidate gene causing benzimidazole resistance. All 40 isolates were found positive for E. granulosus. BLAST-based searches of sequences of each isolate for each gene (nad5 and cytb) confirmed their maximum similarity with the G1 genotype. Overall, high haplotype diversity (Hd nad5 = 1.00; Hd cytb = 0.833) and low nucleotide diversity (π nad5 = 0.00560; π = cytb = 0.00763) was identified based on diversity indices. For both the genes, non-significant values of Tajima's D (nad5 = -0.81734; cytb = -0.80861) and Fu's Fs (nad5 = -1.012; cytb = 0.731) indicate recent population expansion. Bayesian phylogeny-based results of nad5 and cytb sequences confirmed their genotypic status as distinct from other Echinococcus species. This study shed light on the status of benzimidazole resistance in Echinococcus granulosus for the very first time from Pakistan. The findings of this study will significantly add in the information available on genetic diversity of Echinoccous granulosus based on cytb and nad5 genes sequences.

Genotype Impacts Axial Length Growth in Pseudophakic Eyes of Marfan Syndrome.

Purpose: The purpose of this study was to investigate the relationship between axial length (AL) growth and FBN1 genotype in patients with Marfan syndrome (MFS) after lens surgery and customize the selection of intraocular lens (IOL) power. Methods: Patients with MFS who had lens surgery and primary IOL implantation received panel-based next-generation sequencing (NGS). The rate of axial length growth (RALG) was calculated using pre- and postoperative AL measurements and corrected log10-transformed age. A multivariable regression model of RALG was developed after analyzing the effect of FBN1 genotypes and confounding factors. Results: A total of 139 probands of MFS with a median age at lens surgery of 6.25 years (interquartile range [IQR] = 4.67, 12.50 years) were followed up for a median duration of 2.08 years (IQR = 1.16, 3.00 years). The AL growth curve between the age of 3 and 15 years old was logarithmic. Dominant-negative (DN) variants affecting the disulfide-bridge forming cysteines and the conserved residues for calcium-binding had significantly higher RALG than DN variants affecting other structures (P = 0.001) but comparable to that of haplo-insufficiency variants (P = 1.000). Pre-operative AL (b = 0.563, P = 0.011) and genotype constant (b = 2.603, P = 0.011) were significantly associated with RALG in the final model. A Python-based calculator, Marfan IOL Calculator version 2.0, was programmed using the RALG to predict postoperative AL and customize IOL selection based on the ocular biometric parameters and FBN1 genotype. Conclusions: FBN1 genotype impacted the growth of AL in patients with MFS after IOL implantation. Knowing the FBN1 genotype could help cataract surgeons to customize IOL selection.

Genetic variation and population structure of Fasciola hepatica: an in silico analysis.

Fasciola hepatica is a trematode leading to heavy economic setbacks to the livestock sector globally. The population's genetic information and intimate kinship level are frequently assessed using analysis of mitochondrial DNA. In this analysis, we retrieved cox1 (n = 247) and nad1 (n = 357) sequences of F. hepatica from the NCBI GenBank database and aligned the sequences with the respective reference sequences using MEGA software. The median joining network was drawn using PopArt software while neutrality and diversity indices were estimated with the help of DnaSp software. Neighbor-joining phylogenetic tree was constructed using the MEGA software package. A total of 46 and 98 distinctive haplotypes were observed for cox1 and nad1 genes, respectively. Diversity indices indicated high haplotype and nucleotide diversities in both genes. Positive Tajima's D and Fu's Fs values were found for the entire population of both the genes under study. The cox1 and nad1 gene segments in this study showed high Tajima's D values, suggesting a low likelihood of future population growth. The Tajima's D value of the nad1 gene sequence is lower (2.14910) than that of the cox1 gene sequence (3.40314), which suggests that the former is growing at a slower rate. However, the region-wise analysis revealed that both the cox1 and nad1 genes showed deviation from neutrality suggesting a recent population expansion as a result of an excess of low-frequency polymorphism. Furthermore, the overall host-wise analysis showed positive and significant Tajima's D values for the cox1 and nad1 gene sequences. To the best of our knowledge, this is the first attempt to provide insights into genetic variations and population structure of F. hepatica at a global scale using cox1 and nad1 genes. Our findings suggest the existence of specific variants of F. hepatica in different parts of the world and provide information on the molecular ecology of F. hepatica. The results of this study also mark a critical development in upcoming epidemiological investigations on F. hepatica and will also contribute to understanding the global molecular epidemiology and population structure of F. hepatica.

Pancreatic ductal adenocarcinoma with synchronous and metachronous hepatic metastasis predicted by contrast-enhanced ultrasound.

Background: Contrast-enhanced ultrasound (CEUS) has proven valuable in diagnosing benign and malignant pancreatic diseases, but its value in evaluating hepatic metastasis remains to be further explored. This study investigated the relationship between CEUS features of pancreatic ductal adenocarcinoma (PDAC) and concomitant or recurrent liver metastases after treatment. Methods: This retrospective study included 133 participants with PDAC who were diagnosed with pancreatic lesions with CEUS at Peking Union Medical College Hospital from January 2017 to November 2020. According to the CEUS classification methods in our center, all the pancreatic lesions were classified as either with rich or poor blood supply. Additionally, quantitative ultrasonographic parameters were measured in the center and periphery of all pancreatic lesions. CEUS modes and parameters of the different hepatic metastasis groups were compared. The diagnostic performance of CEUS was calculated for diagnosing synchronous and metachronous hepatic metastasis. Results: The proportions of rich blood supply and poor blood supply were 46% (32/69) and 54% (37/69), respectively, in the no hepatic metastasis group; 42% (14/33) and 58% (19/33), respectively, in the metachronous hepatic metastasis (MHM) group; and 19% (6/31) and 81% (25/31), respectively, in the synchronous hepatic metastasis (SHM) group. The wash-in slope ratio (WIS ratio) between the center of the lesion and around the lesion and peak intensity ratio (PI ratio) between the center of the lesion and around the lesion had higher values in the negative hepatic metastasis group (P<0.05). In predicting synchronous and metachronous hepatic metastasis, the WIS ratio had the best diagnostic performance. The sensitivity (SEN), specificity (SPE), accuracy (ACC), positive predictive value (PPV), and negative predictive value (NPV) were 81.8%, 95.7%, 91.2%, 90.0%, and 91.7%, respectively, for MHM; and 87.1%, 95.7%, 93.0%, 90.0%, and 94.3%, respectively, for SHM. Conclusions: CEUS would be helpful in image surveillance for synchronous or metachronous hepatic metastasis of PDAC.

Past and present of diagnosis of echinococcosis: A review (1999-2021).

The larval forms of taeniid cestodes belonging to the genus Echinococcus are the source of the zoonotic infection known as echinococcosis. Alveolar and cystic echinococcosis are caused by Echinococcus multilocularis and Echinococcus granulosus (s. s), respectively. It is endemic in several regions of the world. In this systematic review, we describe diagnosis, and the species (human, canids, livestock, and small rodents) affected by cystic (CE) and alveolar echinococcosis (AE). From 1999 to 2021, we searched the online directory through PubMed, SCOPUS, Web of Science, and google scholar. Among the 37,700 records found in the online databases, 187 publications met our eligibility requirements. The majority of investigations employed a range of diagnostic methods, such as ELISA, imaging, copro-PCR, necropsy or arecoline hydrobromide purgation, morphological cestode confirmation, and fecal sieving/flotation to detect and confirm Echinococcus infection. ELISA was the most commonly used method followed by PCR, and imaging. The research team retrieved data describing the incidence or assessment of the diagnostic test for E. multilocularis in humans (N = 99), canids (N = 63), small ruminants (N = 13), large ruminants (N = 3), camel (N = 2), pigs (N = 2) and small mammals (N = 5). This study was conducted to explore the diagnostic tools applied to detect echinococcosis in humans as well as animals in prevalent countries, and to report the characteristic of new diagnostic tests for disease surveillance. This systematic review revealed that ELISA (alone or in combination) was the most common method used for disease diagnosis and diagnostic efficacy and prevalence rate increased when recombinant antigens were used. It is highly recommended to use combination protcols such as serological with molecular and imaging technique to diagnose disease. Our study identified scarcity of data of reporting echinococcosis in humans/ animals in low-income or developing countries particularly central Asian countries. Study reports in small rodents indicate their role in disease dissemination but real situation in these host is not reflected due to limited number of studies. Even though echinococcosis affects both public health and the domestic animal sector, therefore, it is important to devise new and strengthen implementation of the existing monitoring, judging, and control measures in this estimate.

Update on the genetic diversity and population structure of Echinococcus granulosus in Gansu Province, Tibet Autonomous Region, and Xinjiang Uygur Autonomous Region, Western China, inferred from mitochondrial cox1, nad1, and nad5 sequences.

The identification of additional Echinococcus granulosus sensu lato (s.l.) complex species/genotypes in recent years raises the possibility that there might be more variation among this species in China than is currently understood. The aim of this study was to explore intra- and inter-species variation and population structure of Echinococcus species isolated from sheep in three areas of Western China. Of the isolates, 317, 322, and 326 were successfully amplified and sequenced for cox1, nad1, and nad5 genes, respectively. BLAST analysis revealed that the majority of the isolates were E. granulosus s.s., and using the cox1, nad1, and nad5 genes, respectively, 17, 14, and 11 isolates corresponded to Elodea canadensis (genotype G6/G7). In the three study areas, G1 genotypes were the most prevalent. There were 233 mutation sites along with 129 parsimony informative sites. A transition/transversion ratio of 7.5, 8, and 3.25, respectively, for cox1, nad1, and nad5 genes was obtained. Every mitochondrial gene had intraspecific variations, which were represented in a star-like network with a major haplotype with observable mutations from other distant and minor haplotypes. The Tajima's D value was significantly negative in all populations, indicating a substantial divergence from neutrality and supporting the demographic expansion of E. granulosus s.s. in the study areas. The phylogeny inferred by the maximum likelihood (ML) method using nucleotide sequences of cox1-nad1-nad5 further confirmed their identity. The nodes assigned to the G1, G3, and G6 clades as well as the reference sequences utilized had maximal posterior probability values (1.00). In conclusion, our study confirms the existence of a significant major haplotype of E. granulosus s.s. where G1 is the predominant genotype causing of CE in both livestock and humans in China.

Machine learning-based automated sponge cytology for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction: a nationwide, multicohort, prospective study.

BACKGROUND: Oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction have a dismal prognosis, and early detection is key to reduce mortality. However, early detection depends on upper gastrointestinal endoscopy, which is not feasible to implement at a population level. We aimed to develop and validate a fully automated machine learning-based prediction tool integrating a minimally invasive sponge cytology test and epidemiological risk factors for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction before endoscopy. METHODS: For this multicohort prospective study, we enrolled participants aged 40-75 years undergoing upper gastrointestinal endoscopy screening at 39 tertiary or secondary hospitals in China for model training and testing, and included community-based screening participants for further validation. All participants underwent questionnaire surveys, sponge cytology testing, and endoscopy in a sequential manner. We trained machine learning models to predict a composite outcome of high-grade lesions, defined as histology-confirmed high-grade intraepithelial neoplasia and carcinoma of the oesophagus and oesophagogastric junction. The predictive features included 105 cytological and 15 epidemiological features. Model performance was primarily measured with the area under the receiver operating characteristic curve (AUROC) and average precision. The performance measures for cytologists with AI assistance was also assessed. FINDINGS: Between Jan 1, 2021, and June 30, 2022, 17 498 eligible participants were involved in model training and validation. In the testing set, the AUROC of the final model was 0·960 (95% CI 0·937 to 0·977) and the average precision was 0·482 (0·470 to 0·494). The model achieved similar performance to consensus of cytologists with AI assistance (AUROC 0·955 [95% CI 0·933 to 0·975]; p=0·749; difference 0·005, 95% CI, -0·011 to 0·020). If the model-defined moderate-risk and high-risk groups were referred for endoscopy, the sensitivity was 94·5% (95% CI 88·8 to 97·5), specificity was 91·9% (91·2 to 92·5), and the predictive positive value was 18·4% (15·6 to 21·6), and 90·3% of endoscopies could be avoided. Further validation in community-based screening showed that the AUROC of the model was 0·964 (95% CI 0·920 to 0·990), and 92·8% of endoscopies could be avoided after risk stratification. INTERPRETATION: We developed a prediction tool with favourable performance for screening of oesophageal squamous cell carcinoma and adenocarcinoma of the oesophagogastric junction. This approach could prevent the need for endoscopy screening in many low-risk individuals and ensure resource optimisation by prioritising high-risk individuals. FUNDING: Science and Technology Commission of Shanghai Municipality.

Morphometric Assessment of the Ciliary Body in Patients With Marfan Syndrome and Ectopia Lentis: A Quantitative Study Using Ultrasound Biomicroscopy.

PURPOSE: To explore the biometric characteristics of the ciliary body in patients with Marfan syndrome (MFS) and ectopia lentis (EL). DESIGN: Cross-sectional study. METHODS: Seventy-two consecutive patients with MFS and EL and 72 nondiseased control subjects were recruited. Ciliary body biometric parameters such as ciliary muscle cross-sectional area at 2000 µm from the scleral spur (CMA2000), ciliary muscle thickness at 1000 µm from the scleral spur (CMT1000), and maximum ciliary body thickness (CBTmax) were measured from multiple directions with ultrasound biomicroscopy (UBM). The relationship between ciliary body parameters and other ocular characteristics was also evaluated. RESULTS: Average CMA2000, CMT1000, and CBTmax were 0.692 ± 0.015 mm2, 0.405 ± 0.010 mm, and 0.855 ± 0.023 mm in eyes of patients with MFS, respectively, and were significantly smaller than these values in control subjects (all P < .001). The prevalence of ciliary body thinning was 22.2% in the MFS group vs 0 in the control group (P < .001); eyes with more severe EL had smaller CMA2000 (P = .050), thinner CMT1000 (P = .022), and shorter CBTmax (P = .015). Patients with microspherophakia (MSP) had even smaller CMA2000 (P = .033) and CMT1000 (P = .044) than those without MSP. The most common subluxation direction was in the superonasal quadrant (n = 25; 39.7%), which probably correlates with the thinnest CMT1000 in the inferotemporal quadrant (P = .005). CONCLUSIONS: Patients with MFS and EL had thinner ciliary muscles, shorter ciliary processes, and a higher prevalence of ciliary body thinning, especially those with MSP. Both the extent and direction of subluxation were associated with ciliary body biometry..

Predicting axial length in patients with Marfan syndrome and ectopia lentis after modified capsular tension ring and intraocular lens implantation.

PURPOSE: To predict the growth of axial length (AL) in patients with Marfan syndrome (MFS) and ectopia lentis (EL). SETTING: Eye and ENT Hospital of Fudan University, Shanghai, China. DESIGN: Consecutive retrospective case series. METHODS: Eyes were evaluated that had modified capsular tension ring and intraocular lens (IOL) implantation. The rate of AL growth (RALG) was calculated using AL divided by log10-transformed age. A multivariate linear regression model of RALG was developed after validation. RESULTS: 128 patients with MFS and EL were enrolled with a median follow-up duration of about 3 years. RALG was independent of age between 3 years and 15 years old ( P = .799) and decreased to 0 thereafter ( P = .878). Preoperative AL was associated with RALG in patients under 15 years old ( P = .003). Beta values for the final model of RALG were as below: intercept (-9.794) and preoperative AL (0.664). The postoperative AL was predicted as: postAL = preAL + RALG × log 10 ([postAge + 0.6]/[preAge + 0.6]). The mean prediction error was -0.003 (95% CI, -0.386 to 0.3791) mm and the mean absolute percentage error was 1.93% (95% CI, 0.73% to 3.14%). A Python-based calculator was developed to use the predicted AL in selecting IOL power and setting undercorrection. CONCLUSIONS: The AL growth of patients with MFS followed a logarithmic pattern and ceased at about age 15. A prediction model of postoperative AL was established for individual MFS patients between 3 and 15 years old, which could potentially optimize the IOL power selection.

Synthesis of C4-Aminated Carbazoles and Their Derivatives via Pd/NBE Chemistry.

Carbazole, as one of the most important organic frameworks, has been used in optoelectronic materials and biochemistry. However, the synthesis of C4-substituted carbazole has always been an unsolved problem. This report describes the one-step synthesis of C4-aminated carbazoles and their derivatives through the series reaction of C-H amination and arylation. The substrate scope is wide. C4-Amino carbazoles substituted by C2, C6, C7, and C8 methyl groups, especially carbazole derivatives of fused rings, pyridine, and dibenzofuran, can be synthesized.

Phylogeny and population structure of Echinococcus granulosus (sensu stricto) based on full-length cytb-nad2-atp6 mitochondrial genes - First report from Sialkot District of Pakistan.

Cystic echinococcosis is a zoonotic disease of livestock having serious economic setbacks. The etiological agents of the disease belong to Echinococcus granulosus sensu lato. Despite of worldwide distribution of the disease, the molecular studies mainly employ amplification of cox1, nad1 and nad5 genes. To further strengthen the knowledge about significance of other molecular markers and to investigate the genetic diversity and population structure of Echinococcus species in Pakistan, the current study was designed in which full length mitochondrial cytb, atp6 and nad2 genes were amplified. Based on BLAST searches of the generated cytb, atp6 and nad2 gene sequences from a total of 18 hydatid cysts collected from cattle, 12 isolates were identified as E. granulousus G3 and 6 as E. granulosus (G1). The phylogeny inferred by the Bayesian method using nucleotide sequences of cytb-atp6-nad2 further confirmed their identity. The diversity indices indicated a high haplotype and a low nucleotide diversity. The negative values of Tajima's D and Fu's Fs test demonstrated deviation from neutrality suggesting a recent population expansion. To the best of our knowledge, the present study described the genetic variation of E. granulosus population for the first time in Pakistan using full-length cytb, atp6 and nad2 mitochondrial genes. The findings on the genetic variation of E. granulosus in Pakistan will constitute useful baseline information for future studies on the prevalence and population structure of E. granulosus based on full-length cytb, atp6 and nad2.

Epidemiological characteristics of a 2019-nCoV outbreak caused by Omicron variant BF.7 in Shenzhen / 中华流行病学杂志

Objective: To explore the epidemiological characteristic of a COVID-19 outbreak caused by 2019-nCoV Omicron variant BF.7 and other provinces imported in Shenzhen and analyze transmission chains and characteristics. Methods: Field epidemiological survey was conducted to identify the transmission chain, analyze the generation relationship among the cases. The 2019-nCoV nucleic acid positive samples were used for gene sequencing. Results: From 8 to 23 October, 2022, a total of 196 cases of COVID-19 were reported in Shenzhen, all the cases had epidemiological links. In the cases, 100 were men and 96 were women, with a median of age, M (Q1, Q3) was 33(25, 46) years. The outbreak was caused by traverlers initial cases infected with 2019-nCoV who returned to Shenzhen after traveling outside of Guangdong Province.There were four transmission chains, including the transmission in place of residence and neighbourhood, affecting 8 persons, transmission in social activity in the evening on 7 October, affecting 65 persons, transmission in work place on 8 October, affecting 48 persons, and transmission in a building near the work place, affecting 74 persons. The median of the incubation period of the infection, M (Q1, Q3) was 1.44 (1.11, 2.17) days. The incubation period of indoor exposure less than that of the outdoor exposure, M (Q1, Q3) was 1.38 (1.06, 1.84) and 1.95 (1.22, 2.99) days, respcetively (Wald χ2=10.27, P=0.001). With the increase of case generation, the number and probability of gene mutation increased. In the same transmission chain, the proportion of having 1-3 mutation sites was high in the cases in the first generation. Conclusions: The transmission chains were clear in this epidemic. The incubation period of Omicron variant BF.7 infection was shorter, the transmission speed was faster, and the gene mutation rate was higher. It is necessary to conduct prompt response and strict disease control when epidemic occurs.

Prevalence, risk factors and first record of mitochondrial cox1 gene-based molecular characterization of Paramphistomum epiclitum from Pakistan.

Parasitic infestations are one of the major threats to the livestock industry in Pakistan. These have a negative impact on the production of domesticated livestock species. Paramphistomes belong to the superfamily Paramphistomoidea and are involved in infecting ruminants all over the world. To date, there was no information on mitochondrial DNA-based molecular characterization of Paramphistomum epiclitum from Pakistan. To close this research gap, this study was designed to provide insights into the epidemiology of Paramphistomum species. Paramphistomum epiclitum isolates were recovered from the rumen of small ruminants slaughtered at an abattoir located in Faisalabad city and animal demographics were recorded. DNA was extracted and mitochondrial cox1 was amplified and sequenced. Prevalence was calculated along with a 95% confidence interval in various groups. The chi-square test was applied to determine the association between different variables under investigation. A phylogenetic tree was constructed based on the Bayesian method. Population diversity indices were calculated using DnaSP 4.5 software. A total of 43 mutations were observed among 7 haplotypes. Negative values of Fu's Fs values, and Tajima's D indicated population expansion. Deworming, season, and grazing were the variables that significantly correlate (p < 0.05) with the prevalence of P. epiclitum. The high prevalence of P. epiclitum demonstrates that more studies are indeed needed to further understand the prevalence and distribution of P. epiclitum in definitive and all potential intermediate hosts in addition to intraspecies variation and relationship with populations from other locations.