Assessment of spillover of antimicrobial resistance to untreated children 7 to 12 years old after mass drug administration of azithromycin for child survival in Niger: a secondary analysis of the MORDOR cluster-randomized trial.

BACKGROUND: The risk of antibiotic resistance is complicated by the potential for spillover effects from one treated population to another. Azithromycin mass drug administration programs report higher rates of antibiotic resistance among treatment arms in targeted groups. This study aims to understand the risk of spillover of antibiotic resistance to non-target groups in these programs. METHODS: Data was used from a cluster-randomized trial comparing the effect of biannual azithromycin and placebo distribution to children 1-59 months on child mortality. Nasopharyngeal samples from untreated children 7-12 years old were tested for genetic determinants of macrolide resistance (primary outcome) and resistance to other antibiotic classes (secondary outcomes). Linear regression was used to compare the community-level mean difference in prevalence by arm at the 24-month timepoint adjusting for baseline prevalence. RESULTS: 1,103 children 7-12 years old in 30 communities were included in the analysis (15 azithromycin, 15 placebo). Adjusted mean differences in prevalence of resistance determinants for macrolides, beta-lactams and tetracyclines were 3.4% (95% CI -4.1% to 10.8%, P-value 0.37), -1.2% (95% CI -7.9% to 5.5%, P-value 0.72), and -3.3% (95% CI -9.5% to 2.8%, P-value 0.61), respectively. CONCLUSIONS: We were unable to demonstrate a statistically significant increase in macrolide resistance determinants in untreated groups in an azithromycin mass drug administration program. While the result might be consistent with a small spillover effect, this study was not powered to detect such a small difference. Larger studies are warranted to better understand the potential for spillover effects within these programs.

Deep learning-based reconstruction enhances image quality and improves diagnosis in magnetic resonance imaging of the shoulder joint.

Background: Accelerated magnetic resonance imaging sequences reconstructed using the vendor-provided Recon deep learning algorithm (DL-MRI) were found to be more likely than conventional magnetic resonance imaging (MRI) sequences to detect subacromial (SbA) bursal thickening. However, the extent of this thickening was not extensively explored. This study aimed to compare the image quality of DL-MRI with conventional MRI sequences reconstructed via conventional pipelines (Conventional-MRI) for shoulder examinations and evaluate the effectiveness of DL-MRI in accurately demonstrating the degree of SbA bursal and subcoracoid (SC) bursal thickening. Methods: This prospective cross-sectional study enrolled 41 patients with chronic shoulder pain who underwent 3-T MRI (including both Conventional-MRI and accelerated MRI sequences) of the shoulder between December 2022 and April 2023. Each protocol consisted of oblique axial, coronal, and sagittal images, including proton density-weighted imaging (PDWI) with fat suppression (FS) and oblique coronal T1-weighted imaging (T1WI) with FS. The image quality and degree of artifacts were assessed using a 5-point Likert scale for both Conventional-MRI and DL-MRI. Additionally, the degree of SbA and SC bursal thickening, as well as the relative signal-to-noise ratio (rSNR) and relative contrast-to-noise ratio (rCNR) were analyzed using the paired Wilcoxon test. Statistical significance was defined as P<0.05. Results: The utilization of accelerated sequences resulted in a remarkable 54.7% reduction in total scan time. Overall, DL-MRI exhibited superior image quality scores and fewer artifacts compared to Conventional-MRI. Specifically, DL-MRI demonstrated significantly higher measurements of SC bursal thickenings in the oblique sagittal PDWI sequence compared to Conventional-MRI [3.92 (2.83, 5.82) vs. 3.74 (2.92, 5.96) mm, P=0.028]. Moreover, DL-MRI exhibited higher detection of SbA bursal thickenings in the oblique coronal PDWI sequence [2.61 (1.85, 3.46) vs. 2.48 (1.84, 3.25) mm], with a notable trend towards significant differences (P=0.071). Furthermore, the rSNRs of the muscle in DL-MRI images were significantly higher than those in Conventional-MRI images across most sequences (P<0.001). However, the rSNRs of bone on Conventional-MRI of oblique axial and oblique coronal PDWI sequences showed adverse results [oblique axial: 1.000 (1.000, 1.000) vs. 0.444 (0.367, 0.523); and oblique coronal: 1.000 (1.000, 1.000) vs. 0.460 (0.387, 0.631); all P<0.001]. Additionally, all DL-MRI images exhibited significantly greater rSNRs and rCNRs compared to accelerated MRI sequences reconstructed using traditional pipelines (P<0.001). Conclusions: In conclusion, the utilization of DL-MRI enhances image quality and improves diagnostic capabilities, making it a promising alternative to Conventional-MRI for shoulder imaging.

Discovery of gefitinib-1,2,3-triazole derivatives against lung cancer via inducing apoptosis and inhibiting the colony formation.

A series of 20 novel gefitinib derivatives incorporating the 1,2,3-triazole moiety were designed and synthesized. The synthesized compounds were evaluated for their potential anticancer activity against EGFR wild-type human non-small cell lung cancer cells (NCI-H1299, A549) and human lung adenocarcinoma cells (NCI-H1437) as non-small cell lung cancer. In comparison to gefitinib, Initial biological assessments revealed that several compounds exhibited potent anti-proliferative activity against these cancer cell lines. Notably, compounds 7a and 7j demonstrated the most pronounced effects, with an IC50 value of 3.94 ± 0.17 µmol L-1 (NCI-H1299), 3.16 ± 0.11 µmol L-1 (A549), and 1.83 ± 0.13 µmol L-1 (NCI-H1437) for 7a, and an IC50 value of 3.84 ± 0.22 µmol L-1 (NCI-H1299), 3.86 ± 0.38 µmol L-1 (A549), and 1.69 ± 0.25 µmol L-1 (NCI-H1437) for 7j. These two compounds could inhibit the colony formation and migration ability of H1299 cells, and induce apoptosis in H1299 cells. Acute toxicity experiments on mice demonstrated that compound 7a exhibited low toxicity in mice. Based on these results, it is proposed that 7a and 7j could potentially be developed as novel drugs for the treatment of lung cancer.

Associations of meeting 24-hour movement behavior guidelines with prescribed eyeglasses/contact lenses among children and adolescents.

BACKGROUND: Vision health is crucial for many aspects of life especially in developing populations such as children and adolescents. However, there is a high proportion of children and adolescents who suffer from visual impairments. Notably, accumulating evidence indicates that meeting the 24-hour movement behaviors (24-HMB) guidelines is associated with positive physical and mental health outcomes in children and adolescents. However, the relationship between being prescribed eyeglasses/contact lenses and meeting the 24-HMB guidelines has yet to be investigated. Thus, this study aimed to address this gap in the existing literature by using the 2021 National Survey of Children's Health (NSCH) dataset. METHODS: In this cross-sectional study, data was retrieved from the 2021 NSCH. A total of 14,193 U.S. children and adolescents aged between 6 and 17 years were included for data analyses. We used items of the NSCH concerning the 24-HMB guidelines (i.e., physical activity, screen time, and sleep duration) and prescription of eyeglasses/contact lenses that were answered by the legal guardian of the children. Binary logistic regression was performed to investigate whether meeting the 24-HMB guidelines is associated with prescription eyeglasses/contact lenses and whether wearing eyeglasses/contact lenses predicts adherence to the 24-HMB guidelines among children and adolescents. RESULTS: More than half of the participants (59.53%) wore eyeglasses/contact lenses and only 8.40% of them met all three of the 24-HMB guidelines. Compared to meeting none of the 24-HMB guidelines, meeting one (OR = 0.76, 95% CI = 0.62-0.93, p = 0.008), two (OR = 0.54, 95% CI = 0.43-0.67, p < 0.001), and all three 24-HMB guidelines (OR = 0.47, 95% CI = 0.34-0.64, p < 0.001) were associated with a lower risk of being prescribed eyeglasses/contact lenses among children and adolescents. CONCLUSIONS: The findings of the current study provided evidence that the prevalence of U.S. children and adolescents aged between 6 and 17 years who wore eyeglasses/contact lenses was relatively high. Furthermore, meeting the 24-HMB guidelines was associated with a lower risk of being prescribed eyeglasses/contact lenses. Future studies focusing on the effects of 24-HMB interventions on vision health among children and adolescents are needed to better inform public health actions.

Taxonomic notes on two antlion genera Holzezus Krivokhatsky, 1992 and Subgulina Krivokhatsky, 1996 (Neuroptera: Myrmeleontidae: Myrmecaelurini) from China.

A little-known antlion genus, i.e., Holzezus Krivokhatsky, 1992, with its type species H. compactus Krivokhatsky, 1992, is first recorded from China based on newly collected specimens from Turpan-Hami region of Xinjiang. In this region, another rare genus Subgulina Krivokhatsky, 1996, with its type species S. kerzhneri Krivokhatsky, 1996, in which the males possess a sac-like structure from the gula, is rediscovered from China. In addition, we briefly discuss the complicated phylogenetic relationships among the genera of Myrmecaelurini and other related lineages with similar habitat preference to the arid areas.

Compensatory growth of Microcystis aeruginosa after copper stress and the characteristics of algal extracellular organic matter (EOM).

Cyanobacterial blooms can impair drinking water quality due to the concomitant extracellular organic matter (EOM). As copper is often applied as an algicide, cyanobacteria may experience copper stress. However, it remains uncertain whether algal growth compensation occurs and how EOM characteristics change in response to copper stress. This study investigated the changes in growth conditions, photosynthetic capacity, and EOM characteristics of M. aeruginosa under copper stress. In all copper treatments, M. aeruginosa experienced a growth inhibition stage followed by a growth compensation stage. Notably, although chlorophyll-a fluorescence parameters dropped to zero immediately following high-intensity copper stress (0.2 and 0.5 mg/L), they later recovered to levels exceeding those of the control, indicating that photosystem II was not destroyed by copper stress. Copper stress influenced the dissolved organic carbon (DOC) content, polysaccharides, proteins, excitation-emission matrix spectra, hydrophobicity, and molecular weight (MW) distribution of EOM, with the effects varying based on stress intensity and growth stage. Principal component analysis revealed a correlation between the chlorophyll-a fluorescence parameters and EOM characteristics. These results imply that copper may not be an ideal algicide. Further research is needed to explore the dynamic response of EOM characteristics to environmental stress.

Synthesis and In Vitro Antitumor Activity Evaluation of Gefitinib-1,2,3-Triazole Derivatives.

In this study, 14 structurally novel gefitinib-1,2,3-triazole derivatives were synthesized using a click chemistry approach and characterized by 1H NMR, 13C NMR and high-resolution mass spectrometry (HRMS). Preliminary cell counting kit-8 results showed that most of the compounds exhibit excellent antitumor activity against epidermal growth factor receptor wild-type lung cancer cells NCI-H1299, A549 and NCI-H1437. Among them, 4b and 4c showed the most prominent inhibitory effects. The half maximal inhibitory concentration (IC50) values of 4b were 4.42 ± 0.24 µM (NCI-H1299), 3.94 ± 0.01 µM (A549) and 1.56 ± 0.06 µM (NCI-1437). The IC50 values of 4c were 4.60 ± 0.18 µM (NCI-H1299), 4.00 ± 0.08 µM (A549) and 3.51 ± 0.05 µM (NCI-H1437). Furthermore, our results showed that 4b and 4c could effectively inhibit proliferation, colony formation and cell migration in a concentration-dependent manner, as well as induce apoptosis in H1299 cells. In addition, 4b and 4c exerted its anti-tumor effects by inducing cell apoptosis, upregulating the expression of cleaved-caspase 3 and cleaved-PARP and downregulating the protein levels of Bcl-2. Based on these results, it is suggested that 4b and 4c be developed as potential new drugs for lung cancer treatment.

Gut Microbiome Diversity and Antimicrobial Resistance After a Single Dose of Oral Azithromycin in Children: A Randomized Placebo-Controlled Trial.

Mass antibiotic distribution to preschool children resulted in alterations of the gut microbiome months after distribution. This individually randomized, placebo-controlled trial evaluated changes in the gut microbiome and resistome in children aged 8 days to 59 months after one dose of oral azithromycin in Burkina Faso. A total of 450 children were randomized in a 1:1 ratio to either placebo or azithromycin. Rectal samples were collected at baseline, 2 weeks, and 6 months after randomization and subjected to DNA deep sequencing. Gut microbiome diversity and normalized antimicrobial resistance determinants for different antibiotic classes were evaluated. Azithromycin decreased gut bacterial diversity (Shannon P < 0.0001; inverse Simpson P < 0.001) 2 weeks after treatment relative to placebo. Concurrently, the normalized abundance of macrolide resistance genetic determinants was 243-fold higher (95% CI: 76-fold to 776-fold, P < 0.0001). These alterations did not persist at 6 months, suggesting that disruptions were transient. Furthermore, we were unable to detect resistance changes in other antibiotic classes, indicating that co-resistance with a single course of azithromycin when treated at the individual level was unlikely.

Marine Streptomyces-Derived Novel Alkaloids Discovered in the Past Decade.

Natural alkaloids originating from actinomycetes and synthetic derivatives have always been among the important suppliers of small-molecule drugs. Among their biological sources, Streptomyces is the highest and most extensively researched genus. Marine-derived Streptomyces strains harbor unconventional metabolic pathways and have been demonstrated to be efficient producers of biologically active alkaloids; more than 60% of these compounds exhibit valuable activity such as antibacterial, antitumor, anti-inflammatory activities. This review comprehensively summarizes novel alkaloids produced by marine Streptomyces discovered in the past decade, focusing on their structural features, biological activity, and pharmacological mechanisms. Future perspectives on the discovery and development of novel alkaloids from marine Streptomyces are also provided.

Semi-Supervised Learning for Multi-Label Cardiovascular Diseases Prediction: A Multi-Dataset Study.

Electrocardiography (ECG) is a non-invasive tool for predicting cardiovascular diseases (CVDs). Current ECG-based diagnosis systems show promising performance owing to the rapid development of deep learning techniques. However, the label scarcity problem, the co-occurrence of multiple CVDs and the poor performance on unseen datasets greatly hinder the widespread application of deep learning-based models. Addressing them in a unified framework remains a significant challenge. To this end, we propose a multi-label semi-supervised model (ECGMatch) to recognize multiple CVDs simultaneously with limited supervision. In the ECGMatch, an ECGAugment module is developed for weak and strong ECG data augmentation, which generates diverse samples for model training. Subsequently, a hyperparameter-efficient framework with neighbor agreement modeling and knowledge distillation is designed for pseudo-label generation and refinement, which mitigates the label scarcity problem. Finally, a label correlation alignment module is proposed to capture the co-occurrence information of different CVDs within labeled samples and propagate this information to unlabeled samples. Extensive experiments on four datasets and three protocols demonstrate the effectiveness and stability of the proposed model, especially on unseen datasets. As such, this model can pave the way for diagnostic systems that achieve robust performance on multi-label CVDs prediction with limited supervision.

Functional, transcriptomic, and lipidomic studies of the choC gene encoding a phospholipid methyltransferase in Aspergillus fumigatus.

IMPORTANCE: This study explored the phospholipid metabolic pathway in A. fumigatus and its relationship with fungal growth, metabolism, and pathogenicity. ChoC, based on its critical roles in many aspects of the fungus and relatively conserved characteristics in filamentous fungi with low similarity with mammalian ones, can be a novel target of new antifungal drugs.

Improved assessment sensitivity of time-varying cavitation events based on wavelet analysis.

Ultrasonic cavitation, characterized by the oscillation or abrupt collapse of cavitation nuclei in response to ultrasound stimulation, plays a significant role in various applications within both industrial and biomedical sectors. In particular, inertial cavitation (IC) has garnered considerable attention due to the resulting mechanical, chemical, and thermal effects. Passive cavitation detection (PCD) has emerged as a valuable technique for monitoring this procedure. While the fast Fourier transform (FFT) is a widely used algorithm to analyze IC-induced broadband noise detected by PCD system, it may not adequately capture the time-varying instability of cavitation due to potential nuclei collapse during ultrasound irradiation. In contrast, the continuous wavelet transform offers a more flexible approach, enabling more sensitive analysis of signals with varying frequencies over time. In this study, nanodiamond (ND) and its derivative, nitro-doped nanodiamond (N-AND), known to possess cavitation potential from previous research, were chosen as the source of cavitation nuclei. The cavitation signals detected by PCD were subjected to both FFT and wavelet analyses, with their results comprehensively compared. This research showcased the feasibility of employing wavelet analysis for effective inertial cavitation evaluation. It provided the advantage of monitoring the temporal evolution of cavitation events in real-time, enhancing sensitivity to weak and unstable cavitation signals, especially those in higher order components (3rd and 4th order). Additionally, it yielded a higher level of precision in determining IC thresholds and doses. Furthermore, the inclusion of time information through wavelet analysis offered insights into the limitations of low-cycle ultrasound in inducing IC. This study introduces a novel perspective for more sensitive and precise cavitation assessment, leveraging time and frequency data from wavelet analysis, and holds promise for effective utilization of cavitation effects while minimizing losses and damages resulting from unintended cavitation events.

Tongue, palatal, hyoid and pharyngeal muscle activity during chewing, swallowing, and respiration.

OBJECTIVE: Chewing, swallowing, and respiration are synchronized oropharyngeal functions. This study aimed to analyze the dynamics and coordination during natural chewing and swallowing in relation to respiratory phases. DESIGN: Eight oropharyngeal muscles in minipigs were recorded using electromyography, X-ray fluoroscopy, and nasopharyngeal dynamics. Chewing cycles and swallowing episodes were analyzed for timing and activity amplitude along respiratory cycles. Digastric and middle pharyngeal constrictor were used as zero-points for timing analysis in chewing cycles and swallowing episodes, respectively. The beginning of these cycles and episodes were used as the zero-point for timing analysis in respiration during feeding. RESULTS: The timing of jaw closing (57.8%) was longer than opening (42.2%) during chewing. Muscle activity occurred 20% later than digastric onsets and 15% earlier than jaw closing phase. Duration of muscle activity was shorter in ipsilateral than contralateral sides except for palatal muscles. Pharyngeal, palatal, and hyoid muscles showed longer durations than tongue muscles in jaw opening (p < 0.05). Palatal and hyoid muscles showed 2-phased activity in chewing while hyoid muscles showed higher amplitude in chewing and swallowing than other muscles. About 80% of the chewing cycles and swallowing episodes occurred in expiration. Nasopharyngeal airflow velocity increased from jaw opening to swallowing while airflow pressure decreased. CONCLUSION: These findings indicate key activity of palatal and pharyngeal muscles mostly in chewing. The respiratory cycle changes in chewing and swallowing simultaneously with the activation of the tongue, palatal, and pharyngeal muscles. These findings will be useful for further understanding the mechanisms in swallowing and breathing disorders.

Tannic acid delaying metabolism of resistant starch by gut microbiota during in vitro human fecal fermentation.

This work investigated the effect of tannic acid on the fermentation rate of resistant starch. It was found that 1.0 and 1.5 µmol/L tannic acid decreased the rate of producing gas and short-chain fatty acids (SCFAs) from fermentation of resistant starch, and 1.5 µmol/mL tannic acid had a more profound effect, which confirmed that tannic acid delayed the metabolism of resistant starch. Moreover, tannic acid significantly inhibited the α-amylase activity during fermentation. On the other hand, tannic acid delayed the enrichment of some starch-degrading bacteria. Besides, fermentation of the resistant starch/tannic acid mixtures resulted in more SCFAs, particularly butyrate, and higher abundance of beneficial bacteria, including Bifidobacterium, Faecalibacterium, Blautia and Dorea, than fermentation of resistant starch after 48 h. Thus, it was inferred that tannic acid could delay the metabolism of resistant starch, which was due to its inhibitory effect on the α-amylase activity and regulatory effect on gut microbiota.

Tissue properties and respiratory kinematics of the tongue base and soft palate in the obese OSA minipig.

Obesity is a common finding and a major pathogenetic factor in obstructive sleep apnea (OSA) in adults. To understand the mechanisms behind this, the present study investigated the tissue properties and respiratory kinematics of the tongue base and soft palate in the obese OSA minipig model. In 4 verified obese/OSA and 3 non-obese/non-OSA control minipigs, MRI fat-weighted images, ultrasound elastography (USE), and sleep video-fluoroscopy (SVF) were performed to quantify the fat composition, tissue stiffness, and respiratory kinematics of the tongue base and soft palate during sedated sleep. The results indicated that the fat composition gradually increased from the rostral to caudal tongue base, particularly in the posterior 1/3 of the tongue base, regardless of the presence of obesity and OSA. However, this trend was not seen in the soft palate and pharyngeal wall. The pharyngeal wall presented the highest fat composition as compared with the tongue base and soft palate. Overall, obese OSA minipigs showed stiffer tongue tissue than the controls, particularly in the rostral region of the tongue in obese Yucatan minipigs. The respiratory moving ranges of the soft palate were greater in both dorsal-ventral and rostral-caudal directions and during both respiratory and expiratory phases in OSA obese than control minipigs, and the largest moving ranges were seen in OSA obese Panepinto minipigs. The moving range of the tongue base was significantly smaller. These results suggest more fat infiltration in the caudal region of the tongue base regardless of the presence of obesity and/or OSA. The greater tissue stiffness of the tongue in obese OSA minipigs may result from altered neuromuscular drive.

Chalcogenide GRIN glasses with high refractive index and large refractive index difference for LWIR imaging.

Gradient refractive index (GRIN) materials utilize an internally tailored refractive index in combination with the designed curvature of the optical element surface, providing the optical designer with additional freedom for correcting chromatic and spherical aberrations. In this paper, new GRIN materials suitable for the second (3-5 µm) and third (8-12 µm) atmospheric windows were successfully developed by the thermal diffusion method based on Ge20As20Se60-xTex series high refractive index glasses, where the maximum refractive index difference (Δn) at 4 µm and 10.6 µm were 0.281 and 0.277, respectively. The diffusion characteristics and refractive index distribution of the GRIN glass were analyzed by Raman characterization. Furthermore, the performance of GRIN singlet and homogeneous singlet in the LWIR band (8 µm, 10.6 µm (primary wavelength), 12 µm) was compared, and the results showed that the GRIN singlet had better chromatic aberration correction and unique dispersion characteristics.

Comparison of door-to-door and fixed-point delivery of azithromycin distribution for child survival in Niger: A cluster-randomized trial.

Recent evidence indicates mass azithromycin distribution reduces under-5 mortality. This intervention is being considered for child survival programs in high mortality sub-Saharan African settings. The delivery approach used in prior studies required a full-time census and distribution team, which is not feasible for most programs. To determine the optimal programmatic approach to delivery, this study aimed to compare treatment coverage, costs, and acceptability of different delivery approaches with existing community health workers (CHWs). This cluster-randomized trial included rural and peri-urban communities in Dosso, Niger (clinicaltrials.gov, NCT04774991). A random sample of 80 eligible communities was randomized 1:1 to biannual door-to-door or fixed-point delivery of oral azithromycin to children 1-59 months old over 1 year. Data analysts alone were masked given the nature of the intervention. The primary outcome was community-level treatment coverage defined as the number of children treated recorded by CHWs divided by the number of eligible children determined using a post-distribution census. Costs were monitored through routine administrative data collection and micro-costing. The census included survey questions on intervention acceptability among caregivers, community leaders, and CHWs. After randomization, 1 community was excluded due to inaccuracies in available administrative data, resulting in 39 communities receiving door-to-door delivery. At the second distribution, community-level mean treatment coverage was 105% (SD 44%) in the door-to-door arm and 92% (SD 20%) in the fixed-point arm (Mean difference 13%, 95% CI -2% to 28%, P-value = 0.08). The total cost per dose delivered was $1.91 in the door-to-door arm and $2.51 in the fixed-point arm. Indicators of acceptability were similar across stakeholder groups in both arms, with most respondents in each group indicating a preference for door-to-door. Overall, door-to-door delivery is the preferred approach to azithromycin distribution in this setting and might reach more children at a lower cost per dose delivered than fixed-point. Trial Registration: clinicaltrials.gov NCT04774991.

Respiratory internal kinematics of the tongue base and soft palate in obese minipigs with obstructive sleep apnea.

It is largely unknown how the tongue base and soft palate deform to alter the configuration of the oropharyngeal airway during respiration. This study is to address this important gap. After live sleep monitoring of 5 Yucatan and 2 Panepinto minipigs to verify obstructive sleep apnea (OSA), 8 and 4 ultrasonic crystals were implanted into the tongue base and soft palate to circumscribe a cubic and square region, respectively. The 3D and 2D dimensional changes of the circumscribed regions were measured simultaneously with electromyographic activity (EMG) of the oropharyngeal muscles during spontaneous respiration under sedated sleep. The results indicated that both obese Yucatan and Panepinto minipigs presented spontaneous OSA, but not in 3 non-obese Yucatan minipigs. During inspiration, the tongue base showed elongation in both dorsal and ventral regions but thinning and thickening in the anterior and posterior regions respectively. The widths showed opposite directions, widening in the dorsal but narrowing in the ventral regions. The soft palate expanded in both length and width. Compared to normal controls, obese/OSA ones showed similar directions of dimensional changes, but the magnitude of change was two times larger in the tongue base and soft palate, and obese/OSA Panepinto minipigs presented 10 times larger changes in all dimensions of both the tongue base and the soft palate. The opposite direction of the respiratory spatial relationship between these two structures was seen in obese/OSA as compared to normal minipigs.

Recurrence of common bile duct stones after choledocholithotomy in elderly patients: risk factor analysis and clinical prediction model development.

Background: The reasons for the recurrence of common bile duct stones (CBDS) in elderly patients after choledocholithotomy are still unclear. This study aims to establish a prediction model for CBDS recurrence by identifying risk factors. Methods: We conducted a retrospective analysis of 1804 elderly patients aged 65 years and above who were diagnosed to have CBDS and were admitted to Nanjing First Hospital between January 1, 2010, and January 1, 2021. According to inclusion and exclusion criteria, 706 patients were selected for the final analysis. The patients were assigned to two groups according to the presence or absence of CBDS recurrence, and their clinical data were then statistically analyzed. Subsequently, a prediction model and nomogram were developed, evaluating effectiveness using the concordance index (C-index). Results: Of the 706 elderly patients, 62 patients experienced CBDS recurrence after surgery, resulting in a recurrence rate of 8.8%. The multivariate Cox analysis showed that prior history of cholecystectomy (hazard ratio [HR] = 1.931, 95% confidence interval [CI]: 1.051-3.547, p = 0.034), white blood cell (WBC) count ≥11.0 × 109/L (HR = 2.923, 95% CI: 1.723-4.957, p < 0.001), preoperative total bilirubin (TBIL) level ≥ 36.5 mmol/L (HR = 2.172, 95% CI: 1.296-3.639, p = 0.003), number of stones ≥2 (HR = 2.093, 95% CI: 1.592-5.294, p = 0.001), maximum stone diameter ≥ 0.85 cm (HR = 1.940, 95% CI: 1.090-3.452, p = 0.024), and T-tube drainage (HR = 2.718, 95% CI: 1.230-6.010, p = 0.013) were independent risk factors of CBDS recurrence in elderly patients after choledocholithotomy. A postoperative CBDS recurrence prediction model was constructed with a C-index value of 0.758 (95% CI: 0.698-0.818) and internal validation value of 0.758 (95% CI: 0.641-0.875). Conclusion: A history of cholecystectomy, WBC count ≥11.0 × 109/L, preoperative TBIL level ≥ 36.5 mmol/L, number of stones ≥2, maximum stone diameter ≥ 0.85 cm, and T-tube drainage are the independent risk factors of CBDS recurrence after choledocholithotomy in elderly patients. Our developed prediction model for CBDS recurrence has good predictive ability and can help predict the prognosis of patients with CBDS.