Development of monoclonal antibodies in tablet form: A new approach for local delivery.

Among the various pharmaceutical forms, tablets offer numerous advantages, like ease of administration, cost-effectiveness in production, and better stability of biomolecules. Beyond these benefits, the tablet form opens up possibilities for alternative routes for the local delivery of biopharmaceuticals such as oral or vaginal administration, thereby expanding the therapeutic applications of these biomolecules and overcoming the inconvenients associated with parenteral administration. However, to date there is limited information on the feasibility of developing biomolecules in the tablet form. In this study, we have evaluated the feasibility of developing monoclonal antibodies in the tablet form while preserving their biological properties. Different excipients and process parameters were studied to assess their impact on the antibody's integrity during tableting. ELISA results show that applying compression pressure up to 100 MPa is not detrimental to the antibody's binding properties when formulated from a lyophilized powder containing trehalose or sucrose as the major excipient. This observation was confirmed with SPR and ultracentrifugation experiments, which demonstrated that neither the binding affinity for both Fc and Fab antibody fragments nor its aggregation rate are affected by the tableting process. After compression, the tablets containing the antibodies have been shown to be stable for 6 months at room temperature.

Decalogue for mastering robotic transanal minimally invasive surgery (rTAMIS).

This manuscript offers a detailed description of our successful tips for mastering transanal robotic surgery. It covers various aspects, including patient positioning, management of abdominal pressures to maintain a stable pneumorectum, platform positioning, camera alignment, trocar positioning to minimize collisions, instruments used, and approaches to tumor resection.

EMLA cream in burns: A systematic review of safety, analgesic efficacy, and effects on burn pathophysiology.

AIM: Management of procedural pain in burn care is challenging. Lidocaine-prilocaine cream 5%, eutectic mixture of local anesthetics (EMLA®), is a widely used, effective local anesthetic cream approved for normal intact skin, genital mucosa for superficial surgical procedures, and debridement of chronic leg ulcers. This comprehensive review aimed to determine the safety, analgesic efficacy, and effects of EMLA on burn pathophysiology to provide evidence-based clinical recommendations for introducing the topical anesthetic into burn care. METHODS: The PRISMA guidelines were followed for conducting a systematic PubMed search to include all relevant preclinical and clinical studies, according to pre-specified eligibility criteria. RESULTS: Fifteen studies were included in a qualitative synthesis, among which nine were human and six were animal studies. To date, safety and pharmacokinetic data on EMLA application in burns have been limited. Nevertheless, human studies indicated that EMLA is safe and provides adequate procedural-pain relief in adults when applied to smaller burns. Caution should be exercised when using EMLA in younger children, as systemic toxicity, pertaining to prilocaine-induced methemoglobinemia, has been reported owing to overdosing (high doses applied over large burn areas). Furthermore, animal studies demonstrate the potential beneficial effects of EMLA on burn pathophysiology such as anti-inflammatory, decreased capillary permeability to plasma proteins and edema formation, and improved tissue perfusion, which are factors that may impact burn wound progression. CONCLUSION: Current data on EMLA use in the management of procedural pain in small burns are sparse but suggest that EMLA is safe and effective in adults. Further clinical pharmacokinetic studies are warranted, especially for application on larger burn areas.

Enhancing local representation learning through global-local integration with functional connectivity for EEG-based emotion recognition.

Emotion recognition based on electroencephalogram (EEG) signals is crucial in understanding human affective states. Current research has limitations in extracting local features. The representation capabilities of local features are limited, making it difficult to comprehensively capture emotional information. In this study, a novel approach is proposed to enhance local representation learning through global-local integration with functional connectivity for EEG-based emotion recognition. By leveraging the functional connectivity of brain regions, EEG signals are divided into global embeddings that represent comprehensive brain connectivity patterns throughout the entire process and local embeddings that reflect dynamic interactions within specific brain functional networks at particular moments. Firstly, a convolutional feature extraction branch based on the residual network is designed to extract local features from the global embedding. To further improve the representation ability and accuracy of local features, a multidimensional collaborative attention (MCA) module is introduced. Secondly, the local features and patch embedded local embeddings are integrated into the feature coupling module (FCM), which utilizes hierarchical connections and enhanced cross-attention to couple region-level features, thereby enhancing local representation learning. Experimental results on three public datasets show that compared with other methods, this method improves accuracy by 4.92% on the DEAP, by 1.11% on the SEED, and by 7.76% on the SEED-IV, demonstrating its superior performance in emotion recognition tasks.

Ecosystem Services Approach in Turnicki National Park Planning: Factors Influencing the Inhabitants' Perspectives on Local Natural Resources and Protected Areas.

Despite changing paradigms in nature conservation, protected areas, such as national parks, remain key tools for nature conservation. Today, protected areas are perceived as socio-ecological systems, therefore using an ecosystem services approach may help in their designation. Here, we focus on the planned Turnicki National Park located in the far eastern part of the Polish Carpathian Mountains and conflict between proponents of the park establishment and local stakeholders. We used an ecosystem services-driven questionnaire survey among local communities to analyze interactions between the perception of ecosystem services and opinions about national parks, and the role of social and economic status in shaping these opinions. We found links between opinions towards national parks and other factors: age, life span in a municipality, level of education, and an average net income. Respondents who perceived benefits from nature were more positive towards national parks in general and the Turnicki National Park specifically; however, those who prioritized provisioning services were more skeptical. Also, we distinguished four Fuzzy-Set Qualitative Comparative Analysis models which describe factors shaping opinions on national parks, respectively. The study has shown that the ecosystem services lens perspective can help in exploring the factors crucial while establishing the protected areas in specific social and economic context. The main implication for the study is careful consideration of the role of national park to protect the local environment in harmony with social needs and economic development.

Emerging role of local treatment in the era of advanced systemic treatment in pancreatic cancer with liver metastasis: A systematic review and meta-analysis.

BACKGROUND: Approximately 50% of pancreatic cancer cases are diagnosed with distant metastases, commonly in the liver, leading to poor prognosis. With modern chemotherapy regimens extending patient survival and stabilizing metastasis, there has been a rise in the use of local treatments. However, the effectiveness for local treatment remains unclear. METHODS: PubMed, Embase, and Cochrane databases were searched for studies reporting the survival outcomes of pancreatic cancer cases with isolated synchronous or metachronous liver metastases who underwent curative-intent local treatment. Hazard ratios were combined using a random-effects model. RESULTS: The full texts of 102 studies were screened, and 14 retrospective studies were included in the meta-analysis. Among patients with synchronous liver metastases, overall survival was significantly better in those who underwent curative-intent local treatment than in those who did not (hazard ratio [HR]: 0.35, 95% confidence interval [CI]: 0.24-0.52). Among patients with metachronous liver metastases, overall survival was also significantly better in those who underwent curative-intent local treatment than in those who did not (HR 0.37, 95% CI: 0.19-0.73). CONCLUSIONS: Curative-intent local treatment may be a feasible option for highly selected pancreatic cancer cases with liver metastases. However, the optimal strategy for local treatments should be explored in future studies.

Land use and spatial contiguity are key driven factors of antibiotic multimedia patterns in the megacity river network.

The widespread spread of antibiotics in the environment poses a growing threat to human health. This study investigated the distribution and fate of antibiotics concerning land use characteristics, hydrological conditions, and spatial contiguity within a megacity river network. Temporally, the average concentrations of twenty antibiotics in water (354 ng/L), suspended particulate matter (SPM) (46 ng/L), and sediment (151 ng/g) during dry season were notably higher than that in the corresponding environment media (water: 127 ng/L, SPM: 2 ng/L, and sediment: 49 ng/g) during the wet season. Moreover, the inter-annual variation of antibiotics in water showed a decreasing trend. Spatially, substantial antibiotic contamination was observed in a human-intensive watershed, particularly in the upstream and central city sections. The macrolides in water were most affected by land use types and hydrological processes. Antibiotic contamination in water exhibited a stronger spatial autocorrelation compared to other media. Nevertheless, the interconnectedness of antibiotic contamination in sediments during the wet season warrants attention, and relevant authorities should enhance environmental monitoring in watersheds with pollution hotspots. Certain antibiotics, such as sulfamethoxazole, enrofloxacin, and florfenicol, were transported via urban rivers to the ocean, potentially posing environmental risks to coastal water quality. Local sources accounted for the predominant portion (>50 %) of most antibiotics in various media. The correlation distances of antibiotics in waters during the wet season could screen ecological risk prioritization in aquatic environments.

Reviewing the science on 50 years of conservation: Knowledge production biases and lessons for practice.

Drawing on 662 studies from 102 countries, we present a systematic review of published empirical studies about site-level biodiversity conservation initiated between 1970 and 2019. Within this sample, we find that knowledge production about the Global South is largely produced by researchers in the Global North, implying a neocolonial power dynamic. We also find evidence of bias in reported ecological outcomes linked to lack of independence in scientific studies, serving to uphold narratives about who should lead conservation. We explore relationships in the sample studies between conservation initiative types, the extent of Indigenous Peoples' and local communities' influence in governance, and reported social and ecological outcomes. Findings reveal positive ecological and social outcomes are strongly associated with higher levels of influence of Indigenous Peoples and local communities and their institutions, implying equity in conservation practice should be advanced not only for moral reasons, but because it can enhance conservation effectiveness.

Comparison of locoregional recurrence risk among nipple-sparing mastectomy, skin-sparing mastectomy, and simple mastectomy in patients with ductal carcinoma in situ: a single-center study.

BACKGROUND: In invasive breast cancer, there are no differences among the mid- and long-term oncological safety results of nipple-sparing mastectomy (NSM), skin-sparing mastectomy (SSM), and simple mastectomy (SM). There are several reports comparing NSM and SSM with SM in the context of ductal carcinoma in situ (DCIS); however, the eligibility criteria vary among institutions, and there are no reports that compare all three surgical methods simultaneously within the same institution. This study aimed to compare the local recurrence and survival rates of the three techniques (NSM, SSM, and SM) in Japanese patients undergoing mastectomy for DCIS. METHODS: Patients undergoing NSM, SSM, or SM at our institution between 2006 and 2015 were identified, and their outcomes were analyzed. RESULTS: The mean follow-up period was 80.4 months (standard deviation [SD]: 37.1 months). NSM was performed in 152 cases, SSM in 49, and SM in 44. Five of 245 patients developed local recurrences. Four of these patients had invasive cancer. The primary endpoints of 5-year cumulative local recurrence were 2.4% (95% confidence interval [CI]: 0.0-5.0) for NSM, 2.2% (95% CI: 0.0-6.3) for SSM, and 0% (95% CI: 0.0-0.0) for SM. There were no significant differences among the 5-year local recurrence rates. CONCLUSIONS: In this single-center, retrospective study, the oncological safety of SSM and NSM for DCIS was comparable to that of conventional SM.

Risk factors for persistent fatal opioid-involved overdose clusters in Massachusetts 2011-2021: a spatial statistical analysis with socio-economic, accessibility, and prescription factors.

BACKGROUND: Fatal opioid-involved overdose rates increased precipitously from 5.0 per 100,000 population to 33.5 in Massachusetts between 1999 and 2022. METHODS: We used spatial rate smoothing techniques to identify persistent opioid overdose-involved fatality clusters at the ZIP Code Tabulation Area (ZCTA) level. Rate smoothing techniques were employed to identify locations of high fatal opioid overdose rates where population counts were low. In Massachusetts, this included areas with both sparse data and low population density. We used Local Indicators of Spatial Association (LISA) cluster analyses with the raw incidence rates, and the Empirical Bayes smoothed rates to identify clusters from 2011 to 2021. We also estimated Empirical Bayes LISA cluster estimates to identify clusters during the same period. We constructed measures of the socio-built environment and potentially inappropriate prescribing using principal components analysis. The resulting measures were used as covariates in Conditional Autoregressive Bayesian models that acknowledge spatial autocorrelation to predict both, if a ZCTA was part of an opioid-involved cluster for fatal overdose rates, as well as the number of times that it was part of a cluster of high incidence rates. RESULTS: LISA clusters for smoothed data were able to identify whether a ZCTA was part of a opioid involved fatality incidence cluster earlier in the study period, when compared to LISA clusters based on raw rates. PCA helped in identifying unique socio-environmental factors, such as minoritized populations and poverty, potentially inappropriate prescribing, access to amenities, and rurality by combining socioeconomic, built environment and prescription variables that were highly correlated with each other. In all models except for those that used raw rates to estimate whether a ZCTA was part of a high fatality cluster, opioid overdose fatality clusters in Massachusetts had high percentages of Black and Hispanic residents, and households experiencing poverty. The models that were fitted on Empirical Bayes LISA identified this phenomenon earlier in the study period than the raw rate LISA. However, all the models identified minoritized populations and poverty as significant factors in predicting the persistence of a ZCTA being part of a high opioid overdose cluster during this time period. CONCLUSION: Conducting spatially robust analyses may help inform policies to identify community-level risks for opioid-involved overdose deaths sooner than depending on raw incidence rates alone. The results can help inform policy makers and planners about locations of persistent risk.

Prevalence and antimicrobial resistance of salmonellae isolated from eggs of local chicken in selected towns of Ethiopia.

BACKGROUND: Salmonellosis is one of the most common food-borne diseases in industrialised and developing countries. In recent year, an increase in antimicrobial resistance among different Salmonella serotypes has been observed. OBJECTIVE: A cross-sectional study was conducted to assess the prevalence and antimicrobial susceptibility of Salmonella isolated from local chicken eggs in four selected towns in Ethiopia. METHODS: A total of 115 eggs were examined to detect Salmonella by using standard microbiological methods. The susceptibilities of the isolates to nine antimicrobials were tested by the Kirby-Bauer disk diffusion method. RESULT: The study revealed that of the 115 eggs examined, 22 (19.1%) were positive for Salmonella of which 14 (12.2%) and 8 (7%) of the isolates were from shells and contents, respectively. The occurrence of Salmonella in egg shells and content and between different altitudes did not differ significantly (p > 0.05). Most isolates were resistant to more than three antimicrobials with a high resistance to kanamycin, ampicillin, nalidixic acid, cotrimoxazole, oxytetracycline and chloramphenicol. CONCLUSION: The results indicate the potential importance of local chicken eggs as source of multiple antimicrobial-resistant salmonellae and the need for proper cooking before consumption. Further studies are required to describe the epidemiology of Salmonella in various agroclimatic zones of Ethiopia.

Comparative efficacy of topical lidocaine, tetracaine, and articaine for post-tonsillectomy pain management in children: a prospective, placebo-controlled study.

BACKGROUND: The most important problem in tonsillectomy is pain in the early postoperative period. OBJECTIVE: We purposed to compare the effects of lidocaine, tetracaine, and articaine application to the peritonsillar bed on post-tonsillectomy pain in children. METHODS: The prospective, placebo-controlled study included 80 patients, ages 3-14, who were scheduled for elective tonsillectomy. Patients were randomly divided into four groups. Group 1 received 0.9% NaCl; group 2 received 2% lidocaine; group 3 received 2% tetracaine; and group 4 received 4% articaine to the tonsillary bed for 5 min just after the operation. All patients were evaluated in terms of pain and pain-related adverse events in the postoperative 24 h. RESULTS: All groups that used local anesthetics had significantly lower pain levels than the control group in the first eight hours (p < .001). Furthermore, the articaine group had a lower pain score than the tetracaine group at the eighth hour (p < .05). The articaine group had a lower pain score at the 16th hour than both the control and tetracaine groups (p < .05). There was no significant difference between the groups at the 24th hour (p > .05). CONCLUSION AND SIGNIFICANCE: We recommend the immediate application of topical articaine to the tonsillar bed following the procedure to enhance postoperative pain management.

Mutation Screening of Dictyostelium Restriction Enzyme-Mediated Integration (REMI) Libraries.

Identifying the mechanisms of action of existing and novel drugs is essential for the development of new compounds for therapeutic and commercial use. Here we provide a technique to identify these mechanisms through isolating mutant cell lines that show resistance to drug-induced phenotypes using Dictyostelium discoideum REMI libraries. This approach provides a robust and rapid chemical-genetic screening technique that enables an unbiased approach to identify proteins and molecular pathways that control drug sensitivity. Mutations that result in drug resistance often occur in target proteins thus identifying the specific protein targets for drugs and bioactive natural products. Following the identification of a list of putative molecular targets user selected compound targets can be analyzed to confirm and validate direct inhibitory effects.

Survival outcomes and failure patterns for oropharyngeal cancers treated with simultaneous integrated boost in intensity modulated radiotherapy (SIB-IMRT) and concurrent chemotherapy.

BACKGROUND: Intensity modulated radiotherapy (IMRT) has become a standard radiotherapy treatment delivery option owing to the advantages it offers in terms of target coverage and organ sparing. Furthermore, the ability to introduce different fractionation for different targets lets us deliver higher doses to the high-risk areas and lower doses to the elective volumes at the same sitting, referred to as simultaneous integrated boost (SIB). In the current study, we intended to retrospectively analyze the clinical outcomes and patterns of the failure of oropharyngeal cancers treated with SIB-IMRT and concurrent chemotherapy at our centre and analyze the factors contributing to poorer outcomes. MATERIAL AND METHODS: Data of oropharyngeal cancer patients treated with SIB-IMRT and concurrent chemotherapy were retrieved from the institutional database. Patient demographic details, histopathological features, staging, treatment details, failure patterns and outcomes were documented. All potential factors were evaluated for outcomes. Radiation was delivered by using the SIB-IMRT technique. High-risk planning target volume (PTV) received 66 Gy in 2.2 Gy/fraction, intermediate and low-risk PTV received 60 Gy and 54 Gy, respectively. Primary endpoint was to assess local control (LC), regional control (RC) and loco-regional control (LRC) rates and secondary end point was to evaluate the survival outcomes - overall survival (OS) and cancer-specific mortality. All survival analyzes were performed using the Kaplan-Meier method. RESULTS: A total of 169 cases were included in the final analysis. The median age was 55 years (range 20-78) with 95.3% males. The base of tongue was the most common primary site. Around 54% cases were node negative with 38% patients having stage IV disease. The local control rates for N0 vs. N+ cases were 74.1 vs. 62.3% (P = 0.046), respectively. Similarly, the 4-year RC rates for N0 vs. N+ cases were 94.4 vs. 83.5% (P = 0.024), respectively. On multivariate analysis, only 4-year RC rates showed significant difference between the two (P = 0.039). No differences were found between T stages in LRC and OS. The 4-year LRC rates for stages 1, 2 vs. 3, 4 were non-significant (69.2 vs. 66.3%; P = 0.178). The 4-year OS rate was 81.3%. The 4-year LC and LRC rates were 67.8 and 89.5%, respectively. There were 54 local and 17 regional failures. The median time to failure was 13 months (range 3.6-82.9). CONCLUSION: SIB-IMRT provides comparable outcomes for oropharyngeal cancers. OS and loco-regional recurrences were significantly worse for nodal positive disease.

Stereotactic Body Radiation Therapy for Clinically Localized Prostate Cancer in Men With Hip Prostheses: A Cautionary Note.

PURPOSE: Stereotactic body radiation therapy (SBRT) has been established as a safe and effective treatment for prostate cancer. SBRT requires high accuracy to reduce treatment margins. Metal hip prostheses create artifacts that distort pelvic imaging and potentially decrease the accuracy of target/organ at risk (OAR) identification and radiation dose calculations. Data on the safety and efficacy of SBRT after hip replacement is limited. This single-institution study sought to evaluate the safety and local control following SBRT for prostate cancer in men with hip replacements. METHODS: 23 patients treated with localized prostate cancer and a history of pre-treatment hip replacement, treated with SBRT from 2007 to 2017 at MedStar Georgetown University Hospital were included in this retrospective analysis. Treatment was administered with the CyberKnife® (Accuray Incorporated, Sunnyvale, CA) at doses of 35 Gy or 36.25 Gy in 5 fractions. The targets and OARs were identified and contoured by a single experienced Radiation Oncologist (SPC). The adequacy of the CT and T2W MRI images for treatment planning was assessed with a three-point scale (good, adequate, or suboptimal). During treatment planning, care was taken to avoid treatment beams that directly traversed the hip prosthesis. Toxicities were recorded and scored using the Common Terminology Criteria for Adverse Events version 4.0 (CTCAE v.4.0). Local recurrence was confirmed by magnetic resonance imaging and/or prostate biopsy. RESULTS: The median follow-up was seven years. The patients were elderly (median age = 71 years) with a high rate of comorbidities (Charlson Comorbidity Index > 2 in 25%). Four patients had bilateral hip replacements. The majority of patients were low to intermediate risk per the D'Amico classification. Around 13% received upfront ADT. In total, 13 patients were treated with 35 Gy, and 10 were treated with 36.25 Gy. The rates of late > Grade 3 GU toxicity and > Grade 2 GI toxicity were 8.6% and 4.3%, respectively. There were no Grade 4 or 5 toxicities. Six patients (26%) developed a local recurrence at a median time of 7.5 years. Of these six patients, four had unilateral hip replacements and two had bilateral. Three underwent salvage cryotherapy and three received salvage ADT. CONCLUSIONS:  In the general population, high-grade toxicities and local recurrences are uncommon following prostate SBRT. However, in this cohort of patients with prior hip replacements, prostate SBRT had higher than expected rates of late toxicity and local recurrence. In the opinion of the authors, such patients should be counseled regarding an elevated risk of late toxicity and local recurrence with prostate SBRT. With its ultrasound guidance, brachytherapy would have the advantage of circumventing the need for MRI/CT-based imaging and thus may represent a preferable radiation alternative in this patient population. If these patients are treated with SBRT, they should be monitored closely for local recurrence so early salvage can be performed. We hope that recent advances in metal artifact reduction techniques and dose-calculation algorithms will improve future outcomes.

Integrating very high resolution environmental proxies in genotype-environment association studies.

Landscape genomic analyses associating genetic variation with environmental variables are powerful tools for studying molecular signatures of species' local adaptation and for detecting candidate genes under selection. The development of landscape genomics over the past decade has been spurred by improvements in resolutions of genomic and environmental datasets, allegedly increasing the power to identify putative genes underlying local adaptation in non-model organisms. Although these associations have been successfully applied to numerous species across a diverse array of taxa, the spatial scale of environmental predictor variables has been largely overlooked, potentially limiting conclusions to be reached with these methods. To address this knowledge gap, we systematically evaluated performances of genotype-environment association (GEA) models using predictor variables at multiple spatial resolutions. Specifically, we used multivariate redundancy analyses to associate whole-genome sequence data from the plant Arabis alpina L. collected across four neighboring valleys in the western Swiss Alps, with very high-resolution topographic variables derived from digital elevation models of grain sizes between 0.5 m and 16 m. These comparisons highlight the sensitivity of landscape genomic models to spatial resolution, where the optimal grain sizes were specific to variable type, terrain characteristics, and study extent. To assist in selecting variables at appropriate spatial resolutions, we demonstrate a practical approach to produce, select, and integrate multiscale variables into GEA models. After generalizing fine-grained variables to multiple spatial resolutions, a forward selection procedure is applied to retain only the most relevant variables for a particular context. Depending on the spatial resolution, the relevance for topographic variables in GEA studies calls for integrating multiple spatial scales into landscape genomic models. By carefully considering spatial resolutions, candidate genes under selection by a more realistic range of pressures can be detected for downstream analyses, with important applied implications for experimental research and conservation management of natural populations.

A novel approach to treating post-stroke depression: administration of Botulinum Toxin A via local facial injection.

Background: Post-stroke depression (PSD) is a frequent complication following a stroke, characterized by prolonged feelings of sadness and loss of interest, which can significantly impede stroke rehabilitation, increase disability, and raise mortality rates. Traditional antidepressants often have significant side effects and poor patient adherence, necessitating the exploration of more suitable treatments for PSD. Previous researchers and our research team have discovered that Botulinum Toxin A (BoNT-A) exhibits antidepressant effects. Therefore, our objective was to assess the efficacy and side effects of BoNT-A treatment in patients with PSD. Methods: A total of 71 stroke patients meeting the inclusion criteria were allocated to the two group. 2 cases were excluded due to severe neurological dysfunction that prevented cooperation and 4 cases were lost follow-up. Ultimately, number of participants in the BoNT-A group (n = 32) and Sertraline group (n = 33). Treatment efficacy was evaluated 1, 2, 4, 8 and 12 weeks post-treatment. Results: There were no significant differences in baseline characteristics between the two groups (p > 0.05). Both groups exhibited comparable treatment efficacy, with fewer side effects observed in the BoNT-A group compared to the Sertraline group. BoNT-A therapy demonstrated significant effects as early as the first week (p < 0.05), and by the 12th week, there was a notable decrease in neuropsychological scores, significantly lower than the baseline level. The analysis revealed significant differences in measurements of the Hamilton Depression Scale (HAMD) (F(770) = 12.547, p = 0.000), Hamilton Anxiety Scale (HAMA) (F(951) = 10.422, p = 0.000), Self-Rating Depression Scale (SDS) (F(1385) = 10.607, p = 0.000), and Self-Rating Anxiety Scale (SAS) (F(1482) = 11.491, p = 0.000). Conclusion: BoNT-A treatment effectively reduces depression symptoms in patients with PSD on a continuous basis.

Efficacy of lateral lymph node dissection for local control of rectal cancer: A multicenter study.

Background: This study aimed to evaluate the efficacy of lateral lymph node dissection (LLND) for rectal cancer by comparing the local control in patients with and without pathological lateral lymph node metastasis (LLNM). Methods: We included 189 patients with rectal cancer who underwent total mesorectal excision and LLND at 13 institutions between 2017 and 2019. Patients with and without pathological LLNM were defined as the pLLNM (+) and (-) groups, respectively. Propensity score-matching helped to balance the basic characteristics of both groups. The incidences of local recurrence (LR) and lateral lymph node recurrence (LLNR) were compared between the groups. Results: In the entire cohort, 39 of the 189 patients had pathological LLNM. The 3-year LR and LLNR rates were 18.3% and 4.0% (p = 0.01) and 7.7% and 3.3% (p = 0.22) in the pLLNM (+) and (-) groups, respectively. After propensity score matching, the data from 62 patients were analyzed. No significant differences in LR or LLNR were observed between both groups. The 3-year LR and LLNR rates were 16.4% and 9.8% (p = 0.46) and 9.7% and 9.8% (p = 0.99) in the pLLNM (+) and (-) groups, respectively. Conclusion: LLND would lead to comparable local control in the pLLNM (+) and (-) groups if the clinicopathological characteristics except for LLNM are similar.

Injectable vancomycin-loaded silk fibroin/methylcellulose containing calcium phosphate-based in situ thermosensitive hydrogel for local treatment of osteomyelitis: Fabrication, characterization, and in vitro performance evaluation.

The conventional treatment of osteomyelitis with antibiotic-loaded nondegradable polymethylmethacrylate (ATB-PMMA) beads has certain limitations, including impeded bone reconstruction and the need for secondary surgery. To overcome this challenge, this study aimed to develop and characterize an injectable vancomycin-loaded silk fibroin/methylcellulose containing calcium phosphate-based in situ thermosensitive hydrogel (VC-SF/MC-CAPs). The VC-SF/MC-CAPs solution can be easily administered at room temperature with a low injectability force of ≤30 N and a high vancomycin (VC) content of ~96%. Additionally, at physiological temperature (37 °C), the solution could transform into a rigid hydrogel within 7 minutes. In vitro drug release performed under both physiological (pH 7.4) and infection conditions (pH 4.5) revealed a prolonged release pattern of VC-SF/MC-CAPs following the Peppas-Sahlin kinetic model. In addition, the released VC from VC-SF/MC-CAPs hydrogels exhibited antibacterial activity against Staphylococcus aureus for a period exceeding 35 days, as characterized by the disk diffusion assay. Furthermore, at pH 7.4, the VC-SF/MC-CAPs demonstrated >60% degradation within 35 days. Importantly, when exposed to physiological pH conditions, CAPs are transformed into bioactive hydroxyapatite, which benefits bone formation. Therefore, VC-SF/MC-CAPs showed significant potential as a local drug delivery system for treating osteomyelitis.