The utilization of cloud-based photo-sharing services has been observed to result in the exposure of thumbnails, thereby engendering a privacy risk. Thumbnail-preserving encryption (TPE) is a method of mitigating this issue by encrypting images while maintaining the usability of thumbnails. Existing sum-preserving encryption (SPE) typically operates on 3-pixel groups, which are not aligned with power-of-two block sizes and can leave residual plaintext when tiling. The proposed mapping is a four-pixel SPE (4px-SPE) mapping, which is a piecewise bijection on 8-bit pixel quadruples that exactly preserves the four-pixel sum and is perfectly invertible. The scheme is integrated into a permutation-substitution TPE framework. It uses a 256-bit master key with deterministic, hash-based key derivation to reproduce per-image and per-block schedules, and to derive per-block keystreams and permutations without relying on plaintext-derived key material. A mathematical proof and exhaustive verification of all 2564 quadruples are provided to validate invertibility under edge cases. Experiments on both grayscale and color images evaluate entropy, histogram behavior, correlation/robustness metrics, and runtime. The results demonstrate high entropy and lossless recovery while maintaining thumbnail usability.
To assess the cost-effectiveness of guideline-directed medical treatments for heart failure with reduced ejection fraction (HFrEF) by performing a network meta-analysis (NMA) of randomized controlled trials (RCTs) feeding a subsequent cost-effectiveness analysis. A random-effects NMA of RCTs was conducted. The primary analysis included only RCTs evaluating drugs in the clinical settings as recommended in the 2021 European Society of Cardiology HF guidelines. Main efficacy outcomes included all-cause mortality (ACM) and total HF hospitalizations (HFH). A decision tree-Markov model was populated with NMA-derived efficacy estimates, quality-of-life data, and costs from United Kingdom (UK, main analysis), as well as Sweden and United States (US) (scenario analyses) healthcare perspectives. 47 RCTs (75,978 patients) were included. The risk of ACM and total HFH decreased with increasing number of pharmacological treatments. In the main (UK) analysis, the greatest benefit was observed with a quadruple therapy including angiotensin receptor-neprilysin inhibitor (ARNI) + β-blocker (BB) + mineralocorticoid receptor antagonist (MRA) + sodium-glucose cotransporter 2 inhibitors (SGLT2i), which resulted as the most cost-effective strategy (12.31 quality-adjusted life-years; net monetary benefit of £338,460; UK perspective). Findings were consistent in Sweden and US. Quadruple therapy with ARNI+BB+MRA+SGLT2i had the highest probability of being the most cost-effective strategy. Our findings might inform future health economic policies and reimbursement decisions, while also considering affordability, budget impact, and implementation feasibility.
Inflammatory bowel disease (IBD) is characterized by chronic intestinal inflammation driven by intestinal barrier disruption, immune dysregulation, and microbiota imbalance. Barrier dysfunction not only aggravates intestinal inflammation but also promotes metabolic liver diseases, such as non-alcoholic steatohepatitis (NASH), through the gut-liver axis. However, current IBD therapies mainly target intestinal oxidative stress and inflammation, with limited efficacy, while NASH treatments focus on the liver, and interventions targeting the gut-liver axis remain limited. Here, we developed a synergistic quadruple intestinal barrier repair system, termed PGaA Gel, based on an inulin hydrogel loaded with gallium-based mesoporous polydopamine nanoparticles (MPDA-Ga) and L-alanyl-l-glutamine (ALG). PGaA Gel was designed to simultaneously restore the physical, chemical, immune, and microbial barriers of the intestine. MPDA-Ga effectively scavenged reactive oxygen species and inhibited pathogenic bacteria, while ALG promoted epithelial regeneration and mucin production. In addition, inulin enhanced intestinal retention and acted as a prebiotic to produce short-chain fatty acids, thereby reinforcing immune tolerance. In mouse models, PGaA Gel exhibited superior efficacy in restoring multidimensional intestinal barrier integrity and significantly alleviated IBD symptoms compared with single-component treatments. Importantly, PGaA Gel also repaired intestinal barrier dysfunction associated with NASH, reduced lipopolysaccharide translocation via the gut-liver axis, and mitigated hepatic inflammation and lipid accumulation. These findings highlight comprehensive intestinal barrier repair as an effective therapeutic strategy for IBD and gut-liver axis-related liver diseases.
Daphnetin is a clinically established coumarin, but its native biosynthetic pathway remains elusive. In this study, a 2-oxoglutarate-dependent dioxygenase (2OGD), AtS8H, was identified that hydroxylates umbelliferone (UMB) to daphnetin , enabling the design of an artificial biosynthetic pathway. However, the pathway efficiency was constrained by the poor solubility of AtS8H and the low catalytic activity of the upstream 2OGD enzyme IbC2'H. To enhance AtS8H solubility, we developed an integrated strategy combining ProteinMPNN-guided sequence redesign with surface charge engineering. The obtained quintuple mutant S8H 2-6 exhibited significantly improved solubility and a 7.2-fold increase in catalytic efficiency. For IbC2'H, we developed a fluorescence-based high-throughput screening method, and a quadruple mutant C6 was obtained by directed evolution, which displayed a 2.7-fold higher kcat and a 3.2 °C improvement in thermal stability. Implementing both engineered enzymes into an optimized Escherichia coli strain enabled the de novo production of daphnetin at a titer of 46 mg/L. This work reports, to the best of our knowledge, the first microbial de novo production of daphnetin from a simple carbon source and demonstrates an integrated enzyme engineering approach that synergistically refines biosynthetic pathways for efficient microbial production.
The VICTOR trial evaluated vericiguat in stable, ambulatory HFrEF patients without recent WHF. Its primary composite endpoint of CV death or HF hospitalization resulted neutral. Yet, a significant reduction in CV mortality was observed. We analyzed the results of the VICTOR trial and put them in the broader context of HFrEF, where anticipating WHF events remains a mandatory task to improve the overall prognosis. We discussed oral diuretic intensification (ODI), that should represent an important aspect to be considered in stable HFrEF patients. Outpatient WHF events are common in well-treated HFrEF patients and future HF trials should consider to regularly capture ODI. Although secondary endpoint analyses should be interpreted as nominal, the reduction in CV mortality in the VICTOR trial cannot be explained solely through prevention of HF progression or an effect on neurohormonal activation and hemodynamic stress. While current evidence for vericiguat is largely derived from patients with recent WHF, as shown in the VICTORIA trial, the findings of the VICTOR trial might provide a rationale for considering vericiguat earlier in the HFrEF treatment pathway, rather than limiting its use exclusively to patients who fail or progress despite quadruple therapy.
This study evaluated the association between midtrimester cervical length (CL) and pregnancy outcomes in low-risk nulliparous and multiparous singletons and assessed whether combining CL with obstetric and medical history improved the prediction of spontaneous preterm birth (sPTB). This multicenter prospective cohort study included singletons without prior sPTB < 34 weeks who had CL measured at 18-22 weeks GA. Outcomes were retrieved through linkage with the national perinatal registry. Primary outcome was sPTB < 37 weeks. Secondary outcomes included PTB rates, NICU admission and perinatal death. Sensitivity and specificity were calculated per CL group. GA at birth was analyzed using Kaplan-Meier curves, and predictors were assessed using multivariable Cox regression with hazard ratios (HR) and 95% confidence intervals (CI). Results are reported separately for nulliparous and multiparous singletons. We retrieved 15,524 pregnancy outcomes following a CL measurement between 2015-2022. In nulliparous singletons (N = 8,078), sPTB < 37 weeks occurred in 31.0%, 8.7%, 9.3%, and 3.5% for CL ≤ 25, 26-30, 31-35, and > 35 mm, respectively. CL ≤ 25 mm identified 7.8% of sPTB < 37 weeks and 31.3% of sPTB < 32 weeks. In multiparous singletons (N = 7,446), rates were 17.2%, 7.9%, 5.2%, and 2.3%, with CL ≤ 25 mm identifying 5.6% of sPTB < 37 weeks and 24.2% of sPTB < 32 weeks. Multivariable Cox regression showed that in nulliparous singletons, only CL categories were associated with sPTB < 37 weeks compared with the reference > 35 mm, with the highest hazard for CL ≤ 25 mm (HR 10.8, 95% CI 6.3-18.8; p < 0.0001). In multiparous singletons, CL ≤ 25, 26-30, and 31-35 mm (p < 0.0001, p = 0.001, p = 0.04), low SES (p = 0.03), smoking (p < 0.0001), and an interpregnancy interval < 6 months (p = 0.02) were significantly associated. This study confirmed the strong inverse correlation between midtrimester CL and sPTB risk, with multivariable regression analyses reinforcing CL as the dominant predictor. Given its ability in identifying those at highest risk, particularly for sPTB < 32 weeks, universal CL measurements should be central to PTB prevention strategies.
Peroxisomes are metabolic organelles in eukaryotes, whose proliferation is regulated by the PEROXIN 11 (PEX11) protein family. Arabidopsis (Arabidopsis thaliana) contains five PEX11 genes that show phylogenetic divergence and distinct expression patterns, but their individual functions remain unclear. Here, we generated a series of higher-order null mutants of the Arabidopsis PEX11 genes. The combined mutation of all PEX11 members within each lineage caused no obvious growth or metabolic defects, pointing to functional redundancy throughout the entire family. However, the pex11abcd quadruple mutant showed impaired fatty acid β-oxidation and photorespiration, along with significantly reduced peroxisome abundance. The pex11abcde quintuple mutant failed to germinate unless its seed coats were manually removed and showed seedling mortality after germination. The results demonstrate that the functions of certain PEX11 proteins in Arabidopsis depend primarily on gene dosage rather than paralog specificity, providing insight into the roles of specific members of this family in maintaining peroxisome abundance and plant viability.
This study aims to assess the efficacy and safety of combining transarterial chemoembolization and hepatic arterial infusion chemotherapy (TACE-HAIC) with targeted immunotherapy in patients with primary hepatocellular carcinoma (HCC) complicated by portal vein tumor thrombus (PVTT). We retrospectively analyzed clinical data from 114 patients with HCC and PVTT treated with either a quadruple-therapy group (TACE-HAIC plus targeted immunotherapy) or a triple-therapy group (TACE plus targeted immunotherapy) at the Affiliated Hospital of Xuzhou Medical University from January 2019 to September 2023. Propensity score matching was applied to these 114 patients. We compared outcomes such as overall survival (OS), progression-free survival (PFS), intrahepatic progression-free survival (IHPFS), PVTT progression-free survival (TTPFS), objective response rate (ORR), disease control rate (DCR), and the incidence of adverse events between the groups. The quadruple-therapy group exhibited a markedly superior ORR of portal vein tumor thrombus relative to the triple-therapy group (P<0.05). However, no significant differences were found between the groups in OS, PFS, IHPFS, or TTPFS (P > 0.05). The combination of TACE-HAIC with targeted immunotherapy (the quadruple-therapy group) is an effective treatment strategy for PVTT, significantly inducing regression of intraportal tumor thrombi and achieving a higher objective response rate.
Oxalate decarboxylase (OXDC) holds substantial potential for applications in food safety, feed supplementation, and environmental remediation. Nevertheless, its industrial production is still restricted by antibiotic-dependent plasmid maintenance, refined substrate consumption, and a high environmental burden. Here, we developed a resource-efficient and sustainable biomanufacturing strategy. A multi-strategy computational framework identified key mutation sites, and a quadruple mutant (K51L-W55Y-D83R-W234Y) exhibited 24 % higher catalytic activity and 42 % improved thermal stability than the wild type. Molecular dynamics analysis attributed these improvements to enhanced dynamic coupling and structural compactness while preserving the Mn2+ catalytic center. To eliminate antibiotic use, a hok/sok stabilization system was introduced for stable plasmid maintenance. Meanwhile, intracellular ATP regeneration mediated by polyphosphate kinase led to a 35.32 % increase in ATP levels, which in turn resulted in a 21.62 % improvement in OXDC titer. We substituted refined nitrogen and carbon sources with agro-industrial residues, enabling cost reduction and improved resource utilization. In a 5 L fed-batch fermentation, the production of OXDC reached 1.132 g/L. Life cycle assessment showed that the optimized process reduced total environmental impacts by 86.9 % compared to the conventional antibiotic-dependent process, with notable reductions in climate change and metal depletion driven by material consumption. Overall, this work establishes a scalable and energy-efficient bioprocess by coupling protein engineering with cellular and process-level optimization, providing a generalizable framework for the sustainable production of energy-intensive recombinant enzymes.
Helicobacter pylori infection remains common worldwide and causes chronic gastritis, peptic ulcer disease, gastric mucosa-associated lymphoid tissue lymphoma, and gastric cancer. Eradication therapy has become less reliable as resistance to clarithromycin, metronidazole, and levofloxacin has reduced the performance of older empiric regimens. Potassium-competitive acid blockers (P-CABs), molecular resistance testing, fecal susceptibility assays, and new antimicrobial strategies have changed treatment selection, but none removes the need to match regimen design to microbial biology and antibiotic activity. This narrative review argues that H. pylori management is shifting from empiric eradication toward mechanism-matched therapy. The framework links gastric niche biology, acid acclimation, adhesion, virulence signaling, immune evasion, resistance mechanisms, acid suppression, and partner-antibiotic selection. Recent randomized trials show the strengths and limits of this approach. Vonoprazan-based regimens improve acid suppression and can outperform proton pump inhibitor-based triple therapy in clarithromycin-resistant infection, but rescue-treatment trials show that potent acid suppression alone is insufficient when the partner antibiotic is poorly matched. Molecular testing-guided therapy and fecal molecular susceptibility testing provide practical ways to align antibiotic selection with resistance mechanisms. Rifasutenizol adds a pathogen-targeted option supported by phase 3 evidence in treatment-naive Chinese patients. Adjunctive and investigational approaches, including probiotics, vaccines, phytochemicals, phage-derived agents, and nanomedicine, should be interpreted as supportive or developmental strategies rather than replacements for validated antimicrobial regimens. A mechanism-matched approach can help clinicians and investigators choose regimens, interpret trial results, and design studies that distinguish failures caused by resistance, inadequate acid suppression, regimen intolerance, and prior antibiotic exposure.
Since the 2020 Korean guidelines for Helicobacter pylori treatment, clarithromycin resistance rates have risen from 17.8% to 33.3%, dual-priming oligonucleotide-based polymerase chain reaction (DPO-PCR)-based tailored therapy has been adopted, and P-CABs have become available. This fourth revision addresses these changes. Nine key questions were addressed through systematic reviews with meta-analyses. Thirteen recommendations were evaluated via modified Delphi process involving 64 experts. Twelve recommendations achieved first-round consensus; one required revision and achieved 73.9% agreement. Key changes: (1) dual-pillar strategy of tailored therapy and empirical quadruple therapy; (2) restricted use of empirical clarithromycin-based triple therapy under specific conditions; (3) removal of sequential therapy; (4) P-CABs as PPI alternatives; (5) expansion of eradication indications to include gastric cancer prevention in H. pylori gastritis and regression of hyperplastic polyps ≤ 10 mm; and (6) positioning of bismuth quadruple therapy as a conditionally recommended first-line empirical option with preference for reservation as salvage therapy, and introduction of modified bismuth quadruple therapy (addition of bismuth to conventional regimens) as an additional first-line empirical option. This fourth revised guideline provides updated, evidence-based recommendations for the diagnosis and treatment of H. pylori infection, reflecting the rapidly changing antibiotic resistance landscape and the introduction of new diagnostic and therapeutic tools in Korea. These guidelines aim to assist clinicians, patients, policymakers, and medical educators in optimizing H. pylori management. They may differ from current medical insurance standards and will be revised further based on emerging evidence.
Global human papillomavirus (HPV) prevalence among women rose significantly from 14% (2019) to 24% (2024), underscoring the need to understand transmission dynamics and public health impact. Although multi-genotype infections are increasingly documented, evidence remains limited on their combined effect on cervical lesion severity and transmission, especially in regional populations. Using clinical datasets from Xiamen, China, this study evaluates co-infection patterns through integrated statistical and dynamical models to quantify associations with histological severity and transmissibility. Data were sourced from positive HPV nucleic acid tests at two hospitals in Xiamen. Genotyping employed multiplex PCR-based flow fluorescence hybridisation. Cumulative link models (CLMs) were used to assess associations between multi-genotype infections and cervical lesion severity. Concurrently, an ordinary differential equation transmission model was developed to estimate reproduction numbers, comparing transmission potential across infection types. Of 1 33 438 samples, 15 939 (11.9%) were HPV-positive, covering 27 genotypes. HPV 16, 52 and 58 were the most prevalent high-risk types. Co-infections involving these genotypes showed strong inter-hospital correlation in pairing patterns (Pearson's r=0.851). Co-infection severity association was context-specific: the number of genotypes predicted severity in the screening population (eg, quadruple infections OR=1.47, 95% CI 1.23 to 1.71, p<0.01) but not in the referral population. Conversely, co-infections exhibited consistently higher relative transmissibility indices in both settings (eg, high-low-risk co-infection median model-derived : 2.57-6.82). HPV co-infection impacts are modulated by patient population: relative transmission potential is broadly elevated, whereas histological severity effects are marked in screening cohorts but minimal in referral groups. Context-aware public health strategies-adapting co-infection screening and interventions to clinical setting-are urged for more effective and efficient disease control.
There is an urgent need for novel drug targets and combination therapies for Mycobacterium tuberculosis. The identification of inhibitors that target the mycobacterial respiratory chain, particularly when used in combination, has emerged as an exciting new avenue for addressing antibiotic resistance. However, the lack of inhibitors for respiratory complexes, possible functional redundancy between homologous enzymes, and a poor knowledge of which complexes, when simultaneously inhibited, have lethal phenotypes, have slowed progress in this space. To address these limitations, we have utilized CRISPR interference (CRISPRi) to identify bioenergetic complexes that are functionally redundant or that, when simultaneously inhibited, lead to cell death. Specifically, single, double, triple, and quadruple gene knockdowns of respiratory chain components were developed to investigate the consequences of transcriptional inhibition on cell viability. In addition to functional redundancy being identified between homologous groups of respiratory enzymes, we identify a network of synthetic lethal interactions, including the demonstration of a synthetic lethal interaction between the terminal oxidase cytochrome bcc-aa3 (i.e., qcrB) and malate-quinone oxidoreductase (mqo). In conclusion, these findings reinforce that interactions between bioenergetic complexes are crucial to the growth of M. tuberculosis and represent promising targets for future combination therapies.IMPORTANCENew drugs and combination therapies are urgently needed to treat infections caused by Mycobacterium tuberculosis. Drugs that target the mycobacterial respiratory chain, particularly when used in combination, have emerged as an exciting new avenue for addressing antibiotic resistance. However, functional redundancy between respiratory enzymes and a poor knowledge of which respiratory complexes are simultaneously inhibited have lethal phenotypes, which have slowed the development of drugs in this field. To address these limitations, we have utilized CRISPR interference (CRISPRi) transcriptional knockdowns to identify respiratory complexes that are functionally redundant or that, when simultaneously inhibited, lead to cell death. This work demonstrates that (i) there is functional redundancy between functionally similar respiratory enzymes and (ii) there is a network of lethal interactions. These findings reinforce that interactions between bioenergetic complexes are crucial to the growth of M. tuberculosis and represent promising targets for future combination therapies.
Rice endosperm, the major edible portion of the grain, plays an important role in regulating blood glucose and preventing intestinal diseases by increasing its resistant starch (RS) content. Previous studies have shown that suppressing amylopectin biosynthesis via genome editing can increase RS content. However, the influence of different Waxy (Wx) allelic backgrounds on RS accumulation in edited lines has not been systematically evaluated. In this study, we used glutinous rice Yunan Heixiangnuo (HXN) with a nonfunctional wx allele and indica rice Yixiang 1B (YX1B) with a weak Wxb allele as backgrounds. We simultaneously knocked out SSSIIIa, SBEI, SBEIIa, and SBEIIb using CRISPR/Cas9, and systematically analyzed changes in RS content, rice quality, and yield traits. The results showed that, in the HXN background, multigene knockout did not significantly alter amylose or RS content but largely maintained favorable eating quality. In contrast, in the YX1B background, quadruple-gene knockout lines exhibited an increase in amylose content from 17.7% to 53.7% and an increase in RS content to 2.48%, representing a 4.35-fold increase over the wild type, while gel consistency and seed-setting rate were significantly reduced. Scanning electron microscopy revealed that multigene knockout markedly remodeled starch granule structure, shifting from dense polygonal granules to loosely packed spherical particles and resulting in a floury endosperm. Collectively, enhancement of RS content through multigene editing was influenced by Wx gene function. Although the wx allele failed to increase RS content, it still participated in the regulation of grain quality and yield traits by modulating starch structure. This study provides a reference for breeding high-RS rice cultivars while balancing yield performance and eating quality.
We sought to determine whether the endoscopic grade of gastric atrophy (according to Kimura-Takemoto) affects the likelihood of successful first-line H. pylori eradication. We conducted a retrospective analysis of consecutive patients hospitalized at Wuhan Fourth Hospital between November 2021 and November 2025. Eligible individuals had a positive urea breath test confirming H. pylori infection, were diagnosed with chronic atrophic gastritis via gastroscopy, received a bismuth-containing quadruple regimen as first-line therapy, and returned for a follow-up breath test at least 4 weeks post-treatment. Prior to therapy (within 28 days), each patient underwent high-definition white-light gastroscopy. Two independent endoscopists, unaware of patient allocation, retrospectively reviewed all images to grade atrophy using the Kimura-Takemoto system. Patients were assigned to either the closed-type (C-type) or open-type (O-type) atrophy group. The primary endpoint was eradication failure, defined as a positive follow-up breath test. Logistic regression (univariate and multivariate) was used to identify factors independently linked to treatment failure. A total of 154 patients completed follow-up and were included. The overall eradication rate was 76.6% (118/154). In the open-type atrophy group (n = 26), the eradication rate was only 42.3% (11/26), significantly lower than the 83.6% (107/128) observed in the closed-type group (P < 0.001). After adjusting for confounders such as body weight and age, multivariate analysis revealed that endoscopic open-type atrophy was independently associated with eradication failure (OR = 8.287, 95% CI: 3.150-21.804, P < 0.001). The extent of endoscopic gastric mucosal atrophy independently predicts a lower efficacy of first-line H. pylori eradication. For patients with Kimura-Takemoto open-type atrophy, clarithromycin-containing quadruple regimens should be used cautiously. Alternative clarithromycin-free regimens (e.g., tetracycline-, metronidazole-, or levofloxacin-based therapies, or high-dose amoxicillin with PPI/vonoprazan) or susceptibility-guided individualized therapy are recommended in clinical practice.
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Fusarium head blight (FHB), caused by Fusarium graminearum, poses a significant threat to global wheat production. F. graminearum-mediated suppression of host immunity is critical for infection, yet the underlying mechanisms remain incompletely understood. Fungal chitin deacetylases (CDAs) are known to modify cell wall chitin, a potent microbe-associated molecular pattern, to evade plant defenses. Here, we investigated the CDA family in F. graminearum and identified four secreted paralogs, FgCDA1-4, that are highly induced during wheat infection. Functional analyses confirmed that all four are potent virulence factors, protecting fungal hyphae from degradation by host proteins and suppressing chitin-triggered immunity, including ROS production and callose deposition. Crucially, genetic analysis of single, double, and quadruple deletion mutants revealed a non-additive functional relationship; the virulence defect in multigene mutants was no greater than that of single-gene mutants, pointing to a coordinated mechanism rather than functional redundancy. We subsequently showed through yeast two-hybrid assays, co-immunoprecipitation, and AlphaFold-based structural modeling that FgCDA1-4 physically interact and are likely to assemble into hetero-oligomeric complexes. Our findings uncover a sophisticated immune evasion strategy where F. graminearum deploys a multi-subunit enzymatic complex to ensure robust virulence. This FgCDA complex represents a novel, high-value target for developing durable FHB resistance.
Disruptions of the superior shoulder suspensory complex (SSSC) represent an uncommon and heterogeneous spectrum of shoulder girdle injuries. Because the available literature is largely limited to case reports, small case series, and technical descriptions, management decisions remain challenging, particularly for double, triple, and quadruple disruption patterns. A clinically oriented synthesis is needed to translate fragmented evidence into practical diagnostic and treatment guidance. The purpose of this narrative review was to synthesize the available literature on SSSC disruptions into a practical diagnostic and treatment framework, supplemented by institutional illustrative cases. Emphasis was placed on injury pattern recognition, stepwise imaging assessment, instability markers, operative decision-making, and patient-specific modifiers, including age, bone quality, comorbidities, and functional demand. A narrative review of the literature was performed, including original articles, case reports, case series, technical notes, review articles, and book chapters addressing single, double, triple, and quadruple SSSC disruptions. Evidence was synthesized according to clinically relevant domains, including mechanism of injury, number of disrupted sites, radiographic and computed tomography (CT) findings, instability markers, operative versus nonoperative indications, fixation principles, and reported outcomes. Institutional cases were included as illustrative examples of the proposed framework rather than as a comparative outcome cohort. Single SSSC disruptions generally preserve ring stability and are commonly suitable for nonoperative management, unless substantial displacement, intra-articular extension, glenoid or scapular neck involvement, or mechanical compromise is present. Double disruptions require careful assessment of ring instability; fixation of one or more dominant unstable components should be considered when there is significant displacement, reduced glenopolar alignment, medial or lateral translation, angulation, persistent acromioclavicular/coracoclavicular instability, or functional instability. Triple and quadruple disruptions are rare and traditionally associated with high-energy trauma and concomitant injuries; however, complex disruption patterns may also occur after low-energy trauma in elderly or osteoporotic patients. CT, particularly with multiplanar and 3-dimensional reconstruction, is central for defining bony injury patterns, instability markers, and surgical planning, whereas magnetic resonance imaging has a selective role in suspected ligamentous injury, occult fracture, or associated soft tissue pathology. SSSC disruptions should be approached as ring injuries rather than as isolated fractures or ligamentous lesions. The practical contribution of this review is a structured diagnostic and treatment algorithm that integrates disruption number, radiographic and CT-based instability markers, selective magnetic resonance imaging, patient physiology, bone quality, functional demand, and selective restoration of stability. This framework may help clinicians avoid missed instability, delayed diagnosis, and undertreatment of complex shoulder girdle injuries.
A growing ageing population in Africa underscores the need to reorient health systems to provide care for non-communicable conditions impacting older populations such as hip fractures. In The Gambia, the number of hip fractures are expected to quadruple for both men and women in the next 30 years. This is comparable to hip fracture incidence rates in other South and West African countries. Moreover, mortality rates post-hip fracture are 2-3 fold higher in populations from the African Region than for those in other high-income countries. Globally, in many countries including in The Gambia, musculoskeletal conditions are treated in a pluralistic medical system by both biomedical healthcare professionals and traditional bone setters (TBS). Further research is required to understand the interactions between these different therapeutic modalities in the treatment of fractures, including hip fractures - a life changing injury. Such evidence is important for developing collaborative initiatives between traditional and biomedical practitioners. This study sought to describe the practices and procedures used by TBS to treat hip fractures and their interactions between with biomedical care in The Gambia. In-depth interviews were conducted with 16 TBS and 38 healthcare professionals involved in hip fracture care provision in both rural and urban regions of the country. Data were analysed using an inductive thematic analysis. TBS used different modalities to identify a hip fracture. Most TBS misidentified and treated hip fractures as dislocations. On account of this, treatment consisted of pulling, massaging, and kneading the limb back into the hip socket. During this process, TBS applied concoctions of herbs and butters followed by splinting and tying the limb. Few TBS provided pain relief medication during treatment and most advised an extensive period of immobilisation of the limb. Follow up visits reviewed recovery. The narratives of both TBS and healthcare professionals further highlighted the informal referral of hip fracture patients from TBS to biomedical care to receive radiographs, analgesia, and for other ailments. While some biomedical healthcare professionals maintained that TBS should have no role in hip fracture care, others noted the importance of regulation of TBS practices and training initiatives. Considering these findings, we propose short-, medium- and long-term recommendations for the integration of traditional and biomedical sectors in the treatment of hip fractures in The Gambia. This includes the need to establish regulatory mechanisms for TBS practices and patient referral pathways between biomedical and TBS care.
This review traces the evolving role of tetracycline in Helicobacter pylori eradication, from an adjunct in bismuth‑based quadruple therapy to a core component of modern vonoprazan‑tetracycline (VT) dual therapy, and identifies key knowledge gaps. We conducted a narrative review of tetracycline‑based regimens, focusing on resistance rates, efficacy, safety, and dosing optimisation. Data were extracted from clinical trials, real‑world studies, meta‑analyses, and systematic reviews, especially those comparing VT with bismuth‑based quadruple therapy. Tetracycline maintains extremely low resistance rates (1.2%-3.3% in China, 2.1% globally). As first-line treatment for penicillin-allergic patients, VT dual therapy achieved an eradication rate of 100% (per-protocol: 95.1% in a real-world study), with treatment-emergent adverse events significantly lower than bismuth-based quadruple therapy (14.0% vs. 48.0%). In patients with prior failure of amoxicillin-containing regimens, VT dual therapy achieved an eradication rate of 90.9%. Key unresolved issues include: lack of direct validation of TID tetracycline dosing in the VT dual therapy context (although TID is non-inferior to QID in bismuth-based quadruple therapy); absence of head-to-head comparisons between VT and VA dual therapy; and insufficient evidence for tetracycline use in special populations such as elderly or renally impaired patients. Current data suggest that, VT dual therapy may represent a safe, simplified, effective option, especially for penicillin‑allergic or treatment‑failure patients. However, optimal tetracycline dosing in VT requires dedicated randomised controlled trials. Future guidelines will need robust evidence from dose‑optimisation studies, comparative trials with VA, and long‑term follow‑up.