Understanding Global Access to Topical Onychomycosis Therapy: A Systematic Review and Meta-Analysis.

INTRODUCTION: Equal access to medicines is crucial to ensuring public health, but access is difficult to measure, especially for infections where changes in infective species make treatment choices highly dynamic. This study investigated if the combination of infection prevalence with medicine efficacy and regulatory availability could access medicines access of topical onychomycosis medicines. METHODS: Two databases, PubMed and Web of Science, were used to identify relevant information published between 1990 and 2019. For the meta-analysis, human onychomycosis investigations using PCR analysis were included. Reviewers independently selected eligible articles, extracted data and assessed the study quality. A random-effects meta-analysis model with a Freeman-Tukey transformation was employed to the PCR data. For the meta-analysis, the global infection trends and regional differences in the infective organisms were determined. RESULTS: Of the 26 studies analysed, the PCR analysis in 18 studies confirmed onychomycosis in about half of the visually suspected cases (55%, CI 43%-67%). Across all 26 studies dermatophytes were the most prevalent infective organism (57%, CI 37%-76%), but a sub-group analysis showed yeasts predominated in females (31%, CI 0%-84%) (p < 0.0001), in fingernail infections (42%, CI 21%-65%) (p < 0.0001) and in arid countries (p < 0.0001). Combining these results with medicine efficacy data showed that residents from 83 of the 92 countries assessed (90%) could not access the most efficacious topical product, and 22% could not access any broad-spectrum agents. Countries in Africa had the poorest access to topical onychomycosis medicines. CONCLUSION: This study identified that access to effective topical products for onychomycosis is a global problem. This issue appeared to be due to under-representation of candida infections in pivotal clinical studies of topical onychomycosis products. A head-to-head multicentre study for topical efinaconazole or a novel broad spectrum topical agent is needed to help resolve these access problems. PROTOCOL REGISTRATION: PROSPERO-CRD42023464744.

Emergent Inflation of the Efimov Spectrum under Three-Body Spin-Exchange Interactions.

We resolve the unexpected and long-standing disagreement between experiment and theory in the Efimovian three-body spectrum of ^{7}Li, commonly referred to as the lithium few-body puzzle. Our results show that the discrepancy arises out of the presence of strong nonuniversal three-body spin-exchange interactions, which enact an effective inflation of the universal Efimov spectrum. This conclusion is obtained from a thorough numerical solution of the quantum mechanical three-body problem, including precise interatomic interactions and all spin degrees of freedom for three alkali-metal atoms. Our results show excellent agreement with the experimental data regarding both the Efimov spectrum and the absolute rate constants of three-body recombination, and in addition reveal a general product propensity for such triatomic reactions in the Paschen-Back regime, stemming from Wigner's spin conservation rule.

[Efficacy and safety analysis of bupivacaine liposome for pericapsular nerve group block for postoperative analgesia in elderly patients with hip replacement].

Objective: To investigate the efficacy and safety of bupivacaine liposome for pericapsular nerve group block (PENGB) for postoperative analgesia in elderly patients with total hip replacement. Methods: A total of 42 elderly patients underwent total hip replacement were selected in the Second Affiliated Hospital of Wenzhou Medical University from May to July in 2023, including 19 males and 23 females, aged (68.8±6.3) years, the American Society of Anesthesiologists (ASA) grade Ⅰ to Ⅲ. They were divided into bupivacaine liposome group (observation group) and levobupivacaine hydrochloride group (control group) according to random number table, with 21 cases in each group. All the patients were anesthetized by lumbar anesthesia combined with PENGB. During PENGB, the observation group was injected with 10 ml (133 mg) bupivacaine liposome+5 ml normal saline, and the control group was injected with 10 ml (75 mg) levobupivacaine hydrochloride+5 ml normal saline. The primary outcome measures included the rest and movement visual analogue scale (VAS) scores at 6, 12, 24, 36, 48, 60, and 72 h after operation, the sufentanil consumption in analgesic pump, the numbers of analgesic pump compressions, and the rates of additional parexib sodium use in ward. The secondary outcome measures were the changes in lower limb muscle strength, the length of hospital stay and the occurrence of adverse reactions. Results: There was no significant difference in the rest and movement VAS scores between the two groups at pre-operation and at 6 h after operation (P>0.05);but the rest and movement VAS scores at 12, 24, 36, 48, 60 and 72 h after operation in observation group were significantly lower than those in control group (P<0.05); the rest and movement VAS scores at 6, 12, 24, 36, 48, 60 and 72 h after operation were lower than those at pre-operation in two group (P<0.05). The consumption of sufentanil in analgesic pump and parexib sodium usage in observation group were lower than those in control group at 12, 24, 36 and 48 h after operation (P<0.05). The total number of analgesic pump compressions, the number of effective compressions and the number of ineffective compressions in 48 h in observation group were lower than those in control group (P<0.05). The muscle strength of the lower limbs of all patients were able to move against gravity at 12 h after operation. The incidence of nausea in 48 h after operation in observation group was 9.5% (2/21), which was lower than 42.9% (9/21) in control group (P=0.014). No postoperative vomiting occurred in all patients. The length of the hospital stay was (9.3±2.2) d in observation group and (8.9±1.9) d in control group, and there was no significant difference between the two groups (P=0.500). Conclusion: Compared with levobupivacaine hydrochloride, liposomal bupivacaine in PENGB provides analgesic effects for up to 72 h after total hip replacement in elderly patients, reduces postoperative opioid and other analgesics usage, decreases the incidence of postoperative nausea, and has a minor effect on lower limb movement without prolonging hospitalization.

[Research advances of natural biomaterials in promoting wound repair].

Acute and chronic wounds seriously threaten patients' life health and quality of life, therefore, wound repair has become a hot topic of research for scholars at home and abroad in recent years. With the development of material science and tissue engineering, more and more biomaterials prepared from natural ingredients were used in basic research and clinical treatment of wound repair. Such biomaterials can be used as templates for wound tissue regeneration to induce autologous cell adhesion and migration, and promote the deposition of extracellular matrix, which have broad clinical application prospects. This paper reviews the characteristics and application advance of natural biomaterials which are popular in the field of wound repair, aiming to provide ideas for the research and development of new wound dressing and tissue engineering skin.

[Influencing factors of mild cognitive impairment among the Chinese elderly: a meta-analysis].

Objective: To conduct a meta-analysis on the influencing factors of mild cognitive impairment (MCI) in the Chinese elderly. Methods: The literature related to the influencing factors of MCI in Chinese elderly population was retrieved through CNKI, Wanfang, VIP, PubMed, Embase and Web of Science databases up to March 13, 2022. Stata17.0 software was used to calculate the combined risk ratio (RR) with the 95% confidence interval (CI), test the heterogeneity, and assess the publication bias. Results: A total of 2 450 articles were retrieved, and 49 articles met the inclusion criteria, including 5 cohort studies and 44 case-control studies. Meta-analysis results showed that male (RR=0.778, 95%CI: 0.696-0.870, I2=73.1), education>6years (RR=0.428, 95%CI: 0.374-0.490, I2=86.9) and regular exercise (RR=0.496, 95%CI: 0.421-0.585, I2=81.5) were protective factors for MCI, while age≥70 years (RR=2.431, 95%CI: 2.086-2.833, I2=79.3), family history of dementia (RR=3.228, 95%CI: 2.140-4.867, I2=0.0), smoking (RR=1.214, 95%CI: 1.098-1.342, I2=78.8), alcohol consumption (RR=1.165, 95%CI: 1.047-1.297, I2=68.2), solitary living (RR=2.816, 95%CI: 2.123-3.736, I2=42.0), insomnia (RR=1.402, 95%CI: 1.093-1.799, I2=41.3), overweight/obesity (RR=1.431, 95%CI: 1.207-1.696, I2=75.9), hypertension (RR=1.731, 95%CI: 1.589-1.886, I2=67.1), hyperlipidemia (RR=1.722, 95%CI: 1.541-1.924, I2=63.9), diabetes mellitus (RR=1.495, 95%CI: 1.341-1.666, I2=71.6), cardiovascular diseases (RR=1.671, 95%CI: 1.446-1.932, I2=74.6) and cerebrovascular diseases (RR=2.309, 95%CI: 2.040-2.613, I2=76.3) were risk factors of MCI. Conclusion: The present study indicates that male, junior high school education or above and regular exercise are protective factors of MCI, while age≥70 years, family history of dementia, smoking, alcohol consumption, living alone, insomnia, overweight/obesity, hypertension, hyperlipidemia, diabetes, cardiovascular diseases and cerebrovascular diseases are risk factors of MCI.

[Comparison of two different methods of rapid expansion combined with maxillary protraction in the treatment of skeletal class â ¢ malocclusion].

Objective: To compare the effect of bone-anchored versus tooth-borne rapid palatal expansion (RPE) combined with maxillary protraction in the treatment of skeletal class Ⅲ patients with maxillary hypoplasia. Methods: Twenty-six skeletal class Ⅲ patients with maxillary hypoplasia in the late mixed or early permanent dentition were selected. All the patients underwent RPE combined with maxillary protraction in the Department of Orthodontics, Nanjing Stomatological Hospital, Medical School of Nanjing University from August 2020 to June 2022. The patients were divided into 2 groups. Thirteen patients were enrolled in the bone-anchored RPE group [4 males and 9 females, aged (10.2±1.7) years] and the others were in the tooth-borne RPE group [5 males and 8 females, aged (10.1±1.0) years]. Ten sagittal linear indices [Y-Is distance (the distance from the incisor edge of the maxillary incisor to the vertical reference axis), Y-Ms distance (the distance from the mesial contact point of the maxillary first molar to the vertical reference axis), the relative distance between the maxillary and mandibular molars, overjet, etc.], 6 vertical linear indices [PP-Ms distance (the distance changes from Ms to the palatal plane), etc.] and 8 angle indices [SN-MP angle (the upper external angle of the intersection of the sella-nasion plane and the mandibular plane), U1-SN angle (the lower internal angle of the intersection of the long axis of the maxillary central incisor and the sella-nasion plane), etc.] were measured on the cephalometric radiographs before and after the treatment. Six coronal indicators (the inclination of the left and right first maxillary molar, etc.) were measured on cone-beam CT images before and after the treatment. The proportion of skeletal and dental factors in the changes of overjet were calculated. The differences of the index changes between groups were compared. Results: After the treatment, the anterior crossbite were corrected in both groups, and classⅠor classⅡ molar relationship were attained. In bone-anchored group, the changes of Y-Is distance, Y-Ms distance and maxillary and mandibular molar relative distance were (3.23±0.70), (1.25±0.34) and (2.54±0.59) mm, respectively, significantly less than those in the tooth-borned group in which the corresponding changes were (4.96±0.97) mm (t=-5.92, P<0.001), (3.12±0.83) mm (t=-7.53, P<0.001) and (4.92±1.35) mm (t=-5.85, P<0.05), respectively. The change of overjet in the bone-anchored group was (4.45±1.25) mm, significantly less than that in the tooth-borned group (6.14±1.29) mm (t=-3.38, P<0.05). Skeletal and dental factors accounted for 80% and 20% of the overjet changes in the bone-anchored group, respectively. While in the tooth-borned group, skeletal and dental factors accounted for 62% and 38% of the overjet changes, respectively. The PP-Ms distance change in the bone-anchored group [(-1.62±0.25) mm] was significantly less than that in the tooth-borned group [(2.13±0.86) mm] (t=-15.15, P<0.001). The changes of SN-MP and U1-SN in the bone-anchored group were -0.95°±0.55° and 1.28°±1.30°, respectively, significantly less than those corresponding indices in the tooth-borned group (1.92°±0.95°, t=-9.43, P<0.001; 7.78°±1.94°, t=-10.04, P<0.001). In the bone-anchored group, the inclination changes of maxillary bilateral first molars in the left and right sides were 1.50°±0.17° and 1.54°±0.19°, significantly less than the corresponding indices in the tooth-borned group (2.26°±0.37°, t=6.47, P<0.001; 2.25°±0.35°, t=6.81, P<0.001). Conclusions: The bone-anchored RPE with maxillary protraction could reduce the adverse tooth compensation effect, including the protrusion of maxillary anterior incisors, the increase of overjet and mandibular plane angle, and the mesial movement, extrusion and buccal inclination of maxillary molars.

[Correlation between intestinal and respiratory flora and their metabolites in a rat pneumoconiosis model].

Objective: Differential flora and differential metabolites shared by the intestinal and respiratory tracts of rats were screened to analyze the possible role of changes in intestinal flora and metabolites in the progression of pneumoconiosis in rats. Methods: In April 2020, 18 SD rats were randomly divided into three groups (control group, coal mine dust group and silica group, 6 in each group) , rats in the coal mine dust group and silica group were perfused with 1 ml of 50 mg/ml coal mine well dust suspension and silica suspension by nontracheal exposure, respectively. While rats in the control group were perfused with an equal dose of sterilized normal saline. Twenty four weeks after dust staining, rat feces, throat swabs, and lung lavages were collected. 16SrDNA gene sequencing and UHPLC-QTOF-MS untargeted metabolomics were used to analyze the flora and metabolites in feces, throat swabs and lung lavage fluid of rats in each group, to screen for shared differential flora and shared differential metabolites in intestinal and respiratory tract, and the correlation analysis between the differential flora and metabolites was performed using Spearman's statistics. Results: Compared with the control group, a total of 9 species shared differential flora between intestinal and respiratory tract were screened at phylum level, and a total of 9 species shared differential genus between intestinal and respiratory tract were screened at genus level in the coal mine dust group, mainly Firmicutes, Actinobacteria, Streptococcus, Lactobacillus, etc. Compared with the control group, a total of 9 shared differential flora were screened at the phylum level, and a total of 5 shared differential genus were screened at the genus level in the silica group, mainly Proteobacteria, Actinobacteria, Allobactera, Mucilaginibacter, etc. Compared with the control group, a total of 7 shared differential metabolites were screened for up-regulation of Stigmatellin, Linalool oxide and Isoleucine-leucine in both intestinal and respiratory tract in the coal mine dust group. Compared with the control group , a total of 19 shared differential metabolites werescreened in the silica group, of which Diethanolamine, 1-Aminocyclopropanecarboxylic acid, Isoleucine-leucine, Sphingosine, Palmitic acid, D-sphinganine, 1, 2-dioleoyl-sn-glycero-3-phosphatidylcholine, and 1-Stearoyl-2-oleoyl-sn-glycerol 3-phosphocholine were up-regulated in both the intestinal and respiratory tract. Conclusion: There is a translocation of intestinal and respiratory flora in pneumoconiosis rats, and rats have an imbalance of lipid metabolism during the progression of pneumoconiosis.

Modeling the charge collection efficiency in the Li-diffused inactive layer of P-type high purity germanium detector.

A model of the Li-diffused inactive layer in P-type high purity germanium detectors is built to describe the transportation of charge carriers and calculate the charge collection efficiency therein. The model is applied to calculate charge collection efficiency of a P-type point-contact germanium detector used in rare event physics experiments and validated in another P-type semi-planar germanium detector. The calculated charge collection efficiency curves are well consistent with measurements for both detectors. Effects of the Li doping processes on the charge collection efficiency are discussed based on the model. This model can be easily extended to other P-type germanium detectors, for instance, the P-type broad-energy Ge detector, and the P-type inverted-coaxial point-contact detector.

[Microbiota structure and diversity in Aedes albopictus at different developmental stages].

OBJECTIVE: To investigate the diversity and composition of microflora in laboratory-reared Aedes albopictus at different developmental stages and larval habitat waters. METHODS: The larval habitat waters and different developmental stages of laboratory-reared A. albopictus were collected, and the V3 and V4 regions of the bacterial 16S rRNA gene were sequenced using Illumina Miseq next-generation sequencing. The abundance and diversity of the microflora were examined using alpha diversity index in A. albopictus at different developmental stages, and the difference in the microflora compositions was compared in A. albopictus at different developmental stages using principal component analysis (PCA). In addition, the species composition and relative abundance of microflora in A. albopictus at different developmental stages were described using histograms and Venn diagrams. RESULTS: A total of 16 phyla, 30 classes, 72 orders, 129 families and 224 genera of bacteria were detected in larval habitat waters and different developmental stages of A. albopictus. The highest bacterial diversity was seen in larval A. albopictus, with Chao index of 125.20 ± 30.48 and Shannon diversity index of 2.04 ± 0.39, which were comparable to those (Chao index of 118.52 ± 15.07 and Shannon diversity index of 2.15 ± 0.30) in larval habitat waters (t = 0.35 and -0.41, both P values > 0.05). The bacterial abundance and evenness were significantly greater in female adults than in male adults (Chao index: 42.50 ± 3.54 vs. 18.50 ± 2.13, t = 8.23, P < 0.05; Shannon diversity index: 1.25 ± 1.67 vs. 0.50 ± 0.05, t = 6.00, P < 0.05). Proteobacteria, Bacteroidota, Actinobacteriota and Finnicutes were four common phyla of bacteria at each developmental stage of A. albopictus, with Proteobacteria dominated at the pupal stage (90.36%), Bacteroidota dominated at the adult stage (46.01% in female adults and 86.11% in male adults), and Actinobacteriota dominated at the larval stage (32.10%). Elizabethkingia and Rahnella 1 were common dominant genera of bacteria at each developmental stage of A. albopictus, with Rahnellal as the major component at the pupal stage (87.56%), Elizabethkingia as the main component at the adult stage (46.01% in female adults and 86.11% in male adults, respectively), and Microbacteria as the dominant bacterial genus at the larval stage (12.11%). In addition, Delftia, Elizabethkingia, Romboutsia, Serratia, Rahnella 1, Enterococcus and Microbacterium were common genera of bacteria at each developmental stage of A. albopictus, with Edaphobaculum dominated at the larval stage (17.54%) and Sphingobacterium dominated in larval habitat waters (13.93%). CONCLUSIONS: There are differences in the composition of symbiotic bacteria at different developmental stages of A. albopictus; however, similar microflora diversity is maintained at the phylum level. The microflora diversity is comparable in larvae and larval habitat waters of A. albopictus.