Escherichia coli (E. coli) is a major cause of urinary tract infections, bacteraemia, and sepsis. CFT073 is a prototypic, urosepsis isolate of sequence type (ST) 73. This laboratory, among others, has shown that strain CFT073 is resistant to serum, with capsule and other extracellular polysaccharides imparting resistance. The interplay of such polysaccharides remains under-explored. This study has shown that CFT073 mutants deficient in lipopolysaccharide (LPS) O-antigen and capsule display exquisite serum sensitivity. Additionally, O-antigen and LPS outer core mutants displayed significantly decreased surface K2 capsule, coupled with increased unbound K2 capsule being detected in the supernatant. The R1 core and O6 antigen are involved in the tethering of K2 capsule to the CFT073 cell surface, highlighting the importance of the R1 core in serum resistance. The dependence of capsule on LPS was shown to be post-transcriptional and related to changes in cell surface hydrophobicity. Furthermore, immunofluorescence microscopy suggested that the surface pattern of capsule is altered in such LPS core mutants, which display a punctate capsule pattern. Finally, targeting LPS biosynthesis using sub-inhibitory concentrations of a WaaG inhibitor resulted in increased serum sensitivity and decreased capsule in CFT073. Interestingly, the dependency of capsule on LPS has been observed previously in other Enterobacteria, indicating that the synergy between these polysaccharides is not just strain, serotype or species-specific but may be conserved across several pathogenic Gram-negative species. Therefore, using WaaG inhibitor derivatives to target LPS is a promising therapeutic strategy to reduce morbidity and mortality by reducing or eliminating surface capsule.

The eye lens is a transparent, ellipsoid tissue in the anterior chamber that is required for the fine focusing of light onto the retina to transmit a clear image. The focusing function of the lens is tied to tissue transparency, refractive index, and biomechanical properties. The stiffness and elasticity or resilience of the human lens allows for shape changes during accommodation to focus light from objects near and far. It has long been hypothesized that changes in lens biomechanical properties with age lead to the loss of accommodative ability and the need for reading glasses with age. However, the cellular and molecular mechanisms that influence lens biomechanical properties and/or change with age remain unclear. Studies of lens stiffness and resilience in mouse models with genetic defects or at advanced age inform us of the cytoskeletal, structural, and morphometric parameters that are important for biomechanical stability. In this review, we will explore whether: 1) tissue level changes, including the capsule, lens volume, and nucleus volume, 2) cellular level alterations, including cell packing, suture organization, and complex membrane interdigitations, and 3) molecular scale modifications, including the F-actin and intermediate filament networks, protein modifications, lipids in the cell membrane, and hydrostatic pressure, influence overall lens biomechanical properties.

Carbapenemase-producing Klebsiella pneumoniae represents a major public health issue globally. Isolates with resistance to the newest drugs, like ceftazidime/avibactam (CZA), are increasingly reported. In this study, we analyzed the evolution of KPC-3-producing sequence type (ST) 512 K. pneumoniae strains isolated at three different times (hospitalization days 45, 56, and 78) from the same patient, two of which were observed in a pericholecystic liver abscess. The three K. pneumoniae isolates (295Kp, 304Kp, and hmv-318Kp) from the same patient were subjected to antimicrobial susceptibility testing, whole-genome sequencing, sedimentation assay, biofilm measurement, serum resistance assay, macrophage phagocytosis, and adhesion assays. KPC-producing isolate hmv-318Kp exhibited carbapenem susceptibility, hypermucoviscous (hmv) colony phenotype and CZA resistance. Virulence markers of hypervirulent Klebsiella were absent. Two non-synonymous mutations were identified in the hmv-318Kp genome comparing with isogenic strains: a single-nucleotide polymorphism (SNP) occurred in the pKpQIL plasmid, changing blaKPC-3 in the blaKPC-31 gene variant, conferring CZA resistance; and a second SNP occurred in the wzc gene of the capsular biosynthesis cluster, encoding a tyrosine kinase, resulting in the F557S Wzc protein mutation. The Klebsiella pneumoniae strain exhibiting an hmv phenotype (hmv-Kp) phenotype has been previously associated with amino acid substitutions occurring in the Wzc tyrosin kinase protein. We observed in vivo evolution of the ST512 strain to CZA resistance and acquisition of hypermucoviscosity. The pathogenetic role of the detected Wzc substitution is not fully elucidated, but other Wzc mutations were previously reported in hmv K. pneumoniae. Wzc mutants may be more frequent than expected and an underreported cause of hypermucoviscosity in K. pneumoniae clinical isolates.
OBJECTIVE: Here we describe the evolution of KPC-3-producing ST512 K. pneumoniae isolated at three different times from the same patient of which the last one, from a biliary abscess, showed CZA resistance by KPC-31 production and manifested hmv colony phenotype. Hypervirulent Klebsiella pneumoniae (hv-Kp) isolates are increasingly reported worldwide. Their hypervirulent traits are associated with the presence of rmpA/A2 genes and an hmv. In this study, we identified an hmv-Kp that lacked the rmpA-D cluster but showed an amino acid substitution in the Wzc tyrosin kinase protein, involved in the capsular biosynthesis. This hmv-Kp strain emerged in vivo and evolved resistance to ceftazidime/avibactam resistance in a liver abscess of a patient. Our findings suggest that wzc mutations may be underreported, making it challenging to distinguish hv-Kp from \"classic\" K. pneumoniae with an hmv phenotype.

BACKGROUND: Klebsiella pneumoniae carbapenemase-producing K pneumoniae (KPC-Kp) bloodstream infections are associated with high mortality. We studied clinical bloodstream KPC-Kp isolates to investigate mechanisms of resistance to complement, a key host defense against bloodstream infection.
METHODS: We tested growth of KPC-Kp isolates in human serum. In serial isolates from a single patient, we performed whole genome sequencing and tested for complement resistance and binding by mixing study, direct enzyme-linked immunosorbent assay, flow cytometry, and electron microscopy. We utilized an isogenic deletion mutant in phagocytosis assays and an acute lung infection model.
RESULTS: We found serum resistance in 16 of 59 (27%) KPC-Kp clinical bloodstream isolates. In 5 genetically related bloodstream isolates from a single patient, we noted a loss-of-function mutation in the capsule biosynthesis gene, wcaJ. Disruption of wcaJ was associated with decreased polysaccharide capsule, resistance to complement-mediated killing, and surprisingly, increased binding of complement proteins. Furthermore, an isogenic wcaJ deletion mutant exhibited increased opsonophagocytosis in vitro and impaired in vivo control in the lung after airspace macrophage depletion in mice.
CONCLUSIONS: Loss of function in wcaJ led to increased complement resistance, complement binding, and opsonophagocytosis, which may promote KPC-Kp persistence by enabling coexistence of increased bloodstream fitness and reduced tissue virulence.

BACKGROUND: Streptococcus pneumoniae serotype 3 remains a problem globally. Malawi introduced 13-valent pneumococcal conjugate vaccine (PCV13) in 2011, but there has been no direct protection against serotype 3 carriage. We explored whether vaccine escape by serotype 3 is due to clonal expansion of a lineage with a competitive advantage.
METHODS: The distribution of serotype 3 Global Pneumococcal Sequence Clusters (GPSCs) and sequence types (STs) globally was assessed using sequences from the Global Pneumococcal Sequencing Project. Whole-genome sequences of 135 serotype 3 carriage isolates from Blantyre, Malawi (2015-2019) were analyzed. Comparative analysis of the capsule locus, entire genomes, antimicrobial resistance, and phylogenetic reconstructions were undertaken. Opsonophagocytosis was evaluated using serum samples from vaccinated adults and children.
RESULTS: Serotype 3 GPSC10-ST700 isolates were most prominent in Malawi. Compared with the prototypical serotype 3 capsular polysaccharide locus sequence, 6 genes are absent, with retention of capsule polysaccharide biosynthesis. This lineage is characterized by increased antimicrobial resistance and lower susceptibility to opsonophagocytic killing.
CONCLUSIONS: A serotype 3 variant in Malawi has genotypic and phenotypic characteristics that could enhance vaccine escape and clonal expansion after post-PCV13 introduction. Genomic surveillance among high-burden populations is essential to improve the effectiveness of next-generation pneumococcal vaccines.

UNASSIGNED: To explore the surgical technique and preliminary safety and aesthetic results of endoscopic removal of injectable Amazingel with/without immediate prepectoral implant-based breast augmentation for patients.
UNASSIGNED: The clinical data of 25 patients who underwent endoscopic removal of injectable Amazingel with/without immediate prepectoral implant-based breast augmentation between April 2020 and January 2024 and met the selection criteria was retrospective analysed. The patients\' age ranged from 33 to 73 years, with a mean of 50.4 years, and the body mass index ranged from 16.8 to 26.6 kg/m 2, with a mean of 21.5 kg/m 2. They were all bilaterally injected with Amazingel, and the time between initial injections and surgery ranged from 17 to 26 years, with a mean of 21.4 years. Early safety was evaluated by the incidence of early postoperative complications, and early aesthetic results were evaluated using Harris scores (including breast shape satisfaction, sensation satisfaction, and elasticity satisfaction) at 3 months after operation.
UNASSIGNED: There were 9 cases underwent Amazingel removal (group A) and 16 cases underwent Amazingel removal with immediate prepectoral implant-based breast augmentation (group B). Intraoperative removal of Amazingel ranged from 808 to 1 285 mL, with a mean of 1 050.7 mL; the mass of the capsule removed ranged from 36 to 169 g, with a mean of 103.6 g; and a gross anatomical prosthesis was used with a median size of 345 mL (range, 315-355 mL). The operation time ranged from 95 to 395 minutes, with a mean of 194.2 minutes; and the cost of the procedure ranged from 8000to 91 000 yuan, with a mean of 33 000 yuan. Patients had a median follow-up time of 22.7 months (range, 3.0-48.1 months). There was 1 case of intraoperative skin burn due to the operation of the electric scalpel, which healed naturally after operation without flap necrosis. There was no adverse conditions such as prosthesis outline showing, ripple sign, and capsular contracture during follow-up; a small amount of Amazingel residue was found in 2 patients at 1 year after operation. The Harris score at 3 months after operation was used to evaluate the early aesthetic results, and the breast shape, elasticity, and sensation satisfaction of group A were lower than group B, but the differences between the two groups were not significant ( P>0.05).
UNASSIGNED: Endoscopic removal of injectable Amazingel with/without immediate prepectoral implant-based breast augmentation is safe in the early stage with good aesthetic results, and it is also recommended that patients who had the indications for combined immediate breast augmentation after removal to rebuild the breast appearance.
UNASSIGNED: 探讨腔镜奥美定取出联合或不联合即刻胸肌前假体植入隆胸的手术方法、早期安全性及美容学效果。.
UNASSIGNED: 回顾分析2020年4月—2024年1月收治且符合选择标准的25例行腔镜奥美定取出联合或不联合即刻胸肌前假体植入隆胸术的患者临床资料。患者年龄33～73岁，平均50.4岁；身体质量指数16.8～26.6 kg/m 2，平均21.5 kg/m 2。均为双侧注射奥美定，初次注射至该次手术时间17～26年，平均21.4年。早期安全性通过术后早期并发症发生率进行评估，早期美容学效果采用术后3个月Harris评分（包括乳房外形满意度、感觉满意度、弹性满意度）进行评估。.
UNASSIGNED: 单纯行奥美定取出9例（A组），奥美定取出联合即刻胸肌前假体植入隆胸16例（B组）。术中取出奥美定808～1 285 mL，平均1 050.7 mL；取出包膜质量36～169 g，平均103.6 g；均使用毛面解剖型假体，大小315～355 mL，中位大小345 mL。手术时间95～395 min，平均194.2 min；手术费用0.8～9.1万元，平均3.3万元。患者均获随访，随访时间3.0～48.1个月，中位时间22.7个月。术中因电刀操作导致皮肤烫伤1例，术后自然愈合，无皮瓣坏死；术后3个月内均未发生术区出血、切口裂开、皮下积气、皮瓣坏死等并发症；随访期间均未出现假体轮廓显现、波纹征、包膜挛缩等不良情况；术后1年复查发现2例患者有少量奥美定残留。术后3个月采用Harris评分评定早期美容学效果，A组乳房外形满意度、感觉满意度、弹性满意度均低于B组，但两组差异无统计学意义（ P>0.05）。.
UNASSIGNED: 腔镜奥美定取出联合或不联合胸肌前假体植入隆胸术，术后早期均安全可靠，且具有良好的美容学效果；对于符合适应证的患者建议在奥美定取出后联合即刻假体植入隆胸术，重塑乳房外形。.

UNASSIGNED: Andrographis paniculata (Burm.f.) Nees has been recommended to relieve symptoms and decrease the severity of COVID-19. The clinical study aimed to investigate the efficacy and safety of A. paniculata ethanolic extract (APE).
UNASSIGNED: The efficacy and safety of APE in asymptomatic or mildly symptomatic COVID-19 patients compared with placebo were investigated through a prospective, double-blind randomized control trial. Patients received APE containing 60 mg of andrographolide, three times a day for five days. WHO progression scale, COVID-19 symptoms, and global assessment evaluated the efficacy and adverse events, liver and renal functions were monitored for safety.
UNASSIGNED: 165 patients completed the study (83 patients in the APE group and 82 patients in the placebo group). The highest WHO progression scale was 4 and COVID-19 symptoms were significantly relieved on the last day of intervention in both groups, with no significant difference between groups. APE significantly relieved headache symptoms on day 1 and olfactory loss symptoms on day 2 compared to placebo. The global assessment showed that 80.7% of patients had total recovery after 5-day treatment with APE. Mild diarrhea was the most common side effect with a high dose that resolved within a few days. No hepatic or renal toxicity was associated with treatment.
UNASSIGNED: APE at 180 mg/day for 5 days did not reduce COVID-19 progression in asymptomatic or mildly afflicted COVID-19 patients, however, it shortened the symptoms of olfactory loss with no adverse effects over 5 days of use.

Isolated volar distal radioulnar joint (DRUJ) dislocation is a rare condition with only a few cases reported in the literature. Its diagnosis is often overlooked in the acute phase, and there is no consensus in its management. We present the case of a 20-year-old male patient with an isolated volar radioulnar dislocation, together with a review of the literature. The aim is to present and summarize the acute management of this condition and propose a therapeutic algorithm.

UNASSIGNED: Clostridioides difficile infections (CDI) continue to pose a challenge for clinicians. Fecal microbiota transplantation (FMT) is an effective treatment option in CDI. Furthermore, recent and ongoing studies suggest potential benefits of FMT in other diseases as well.
UNASSIGNED: We would like to present a novel protocol for encapsulation of lyophilized fecal material. Our method provides with better compliance as well as improved flexibility, storage and safety.
UNASSIGNED: FMT was conducted in 28 patients with an overall success rate of 82,14% using apsules containing lyophilized stool. 16 of patients were given capsules with lessened bacteria counts. The success rate in this group was 93,75%.
UNASSIGNED: The results highlight the still unanswered questions about the mechanism of action and contribute to a wider use of FMT in the clinical praxis and in research.

This study aims to evaluate and determine the correlation between in vitro release and in vivo pharmacokinetics of two extended-release dosage forms of Cilostazol. In vitro release profiles for two dosage forms, tablet and capsule, were analyzed under physiologically mimicked medium conditions using the paddle and basket USP release apparatus. A single-dose, two-period crossover study design in beagle dogs was applied for the pharmacokinetic study. The fed and fast effects were considered for evaluation. Pseudo gastric release medium transfer setup study from pH 1.2 to pH 6.8 (+0.5% SLS) and pH 1.2 to pH 6.8 (+1.0% SLS) demonstrated that Pletaal® SR 200 mg capsules have higher drug release rates than Cilostan® CR 200 mg tablets. Similarly, in vivo study showed Cilostazol concentration in plasma and AUC was lower under the fast state than the fed state. The ratio of least squared geometric mean values, Cmax, AUC0-t, and AUC0-inf of Cilostazol were 2.53-fold, 2.89-fold, and 2.87-fold higher for Pletaal® SR 200 mg capsules compared with Cilostan® CR 200 mg tablets, respectively. Correlation of in vitro/in vivo data indicated that Pletal® SR 200 mg capsules have better release and pharmacodynamic effect than Cilostan® CR 200 mg tablets.