Effectiveness of mouth rinses against COVID-19: a systematic review and network meta-analysis.

OBJECTIVE: This systematic review and network meta-analysis (NMA) comprehensively compared the effectiveness of different mouth rinses in reducing the viral load/infectivity of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) (Part I), alleviating clinical symptoms or severity of disease (Part II), and decreasing the incidence of SARS-CoV-2 infection (Part III). METHODS: Randomized controlled trials (RCTs) and non-randomized controlled trials (NRCTs) with restrictions were searched up to 3rd March 2023. Twenty-three studies (22 RCTs and one NRCT) met the inclusion criteria for this systematic review. RESULTS: Five RCTs (454 patients and nine interventions) in Part I were eligible for NMA. The NMA results showed that, in comparison with no rinse, sodium chloride (NaCl) was the most effective mouth rinse for reducing the viral load, followed by povidone-iodine (PVP-I), ß-cyclodextrin + citrox (CDCM), hydrogen peroxide (HP), chlorhexidine gluconate (CHX), cetylpyridinium chloride (CPC), placebo and hypochlorous acid (HClO). However, these results were not significant. Based on surface under the cumulative ranking curve scores, PVP-I was likely to be the most efficacious mouth rinse for reducing SARS-CoV-2 viral load, followed by CDCM, HP, NaCl, CHX, CPC, placebo, no rinse and HClO. CONCLUSION: Due to heterogeneity of the primary studies, the effectiveness of different mouth rinses to reduce viral infectivity, improve clinical symptoms or prevent SARS-CoV-2 infection remains inconclusive.

Retrocaval Ureter in Children: A Report of Eight Cases.

OBJECTIVE: The aim of this study is to report on our last nine years' experience in the diagnosis and treatment of retrocaval ureter. METHODS: Eight patients with retrocaval ureter were reviewed. Intravenous urography and retrograde pyelography were used for confirming the diagnosis. All of the patients had undergone surgery, one case being done laparoscopically. The mean age of the patients was 9.2 years (range 2 to 13 years). RESULTS: Five patients were boys and three were girls. The clinical manifestations were right flank pain in three (37.5%), gross haematuria in one (12.5%) and urinary tract infection in one (12.5%). Three asymptomatic patients were diagnosed by routine physical examination. All of the patients had Type 2 and right-sided retrocaval ureter. Associated anomalies were seen in none of the patients. Retrocaval ureter is a rare anomaly in the paediatric age group. CONCLUSION: Laparoscopy is a promising method to repair the retrocaval ureter.

Development of a DNA microarray-based multiplex assay of avian influenza virus subtypes H5, H7, H9, N1, and N2.

Outbreaks of highly pathogenic avian influenza have caused considerable economic losses in the poultry industry and have also resulted in human deaths since 2004. Rapid subtyping of highly pathogenic avian influenza viruses(HPAIVs) in clinical specimens is a prerequisite of prompt control of disease and prevention of its spreading. In this study, we describe development of a DNA microarray-based detection and subtyping of HPAIVs in field samples. DNA copies of matrix (M) protein genes for the H5, H7, and H9 subtypes of hemagglutinin (HA) and the N1 and N2 subtypes of neuraminidase (NA) were prepared by RT-PCR and specific primers and then spotted onto aldehyde slides to form DNA microarrays. The HPAIV samples to be tested were subjected to total RNA isolation, RT-PCR with universal primers and Cy3 labeling, and the obtained double-stranded DNAs (targets) were finally hybridized with DNA microarrays (probes). A fluorescent spot on the microarray, detected by scanning indicated positive hybridization, i.e. the involved subtype. The assay was specific as various heterologous viruses or HPAIVs of other subtypes tested were negative. No cross-hybridization among different subtypes could be detected. The assay was more sensitive than RT-PCR and chicken embryo inoculation and could be also used for field samples. Summing up, the assay has proved useful for simultaneous detection and differentiation of main epidemic HPAIV subtypes.

Unusual causes of carpal tunnel syndrome: space occupying lesions.

Space occupying lesions found at surgery caused or contributed to carpal tunnel syndrome in 23 of 779 patients operated for carpal tunnel syndrome from January 1999 to December 2008. The mean age of these 23 patients was 52.9 years, and in patients who had a local swelling or palpable mass, ultrasonography or magnetic resonance imaging (MRI) was done. All had open release of the transverse carpal ligament and lesions were removed. Histopathology showed tophaceous gout in 10 men, tenosynovitis in seven patients and tumors in eight. The tumors included ganglion cysts in two, lipoma in three and fibroma of the tendon sheath in one. The neurological symptoms subsided after surgery in all. In patients with gout, one had an infected wound and another had recurrence of symptoms 1 year after later. Carpal tunnel syndrome caused by a space occupying lesion is rare and more complicated than idiopathic carpal tunnel syndrome.

Comparison of distribution and activity of nanoparticles with short interfering DNA (Dbait) in various living systems.

Introducing small DNA molecules (Dbait) impairs the repair of damaged chromosomes and provides a new method for enhancing the efficiency of radiotherapy in radio-resistant tumors. The radiosensitizing activity is dependent upon the efficient delivery of Dbait molecules into the tumor cells. Different strategies have been compared, to improve this key step. We developed a pipeline of assays to select the most efficient nanoparticles and administration protocols before preclinical assays: (i) molecular analyses of complexes formed with Dbait molecules, (ii) cellular tests for Dbait uptake and activity, (iii) live zebrafish embryo confocal microscopy monitoring for in vivo distribution and biological activity of the nanoparticles and (iv) tumor growth and survival measurement on mice with xenografted tumors. Two classes of nanoparticles were compared, polycationic polymers with linear or branched polyethylenimine (PEI) and covalently attached cholesterol (coDbait). The most efficient Dbait transfection was observed with linear PEI complexes, in vitro and in vivo. Doses of coDbait ten-fold higher than PEI/Dbait nanoparticles, and pretreatment with chloroquine, were required to obtain the same antitumoral effect on xenografted melanoma. However, with a 22-fold lower 'efficacy dose/toxicity dose' ratio as compared with Dbait/PEI, coDbait was selected for clinical trials.

Molecular therapy in support to radiotherapy.

Approximately half of all cancer patients are treated with radiation therapy. However, some tumor cells can escape the lethal effects of irradiation by hypoxia, deregulation of the cell cycle or apoptosis or by increasing their ability to repair the DNA damage induced, resulting in recurrence of disease. In order to overcome these resistance mechanisms, various strategies have been developed. Over the last decade, extensive progress in human genomics and genetic tools has been made. Several methods using DNA or RNA molecules have been developed to target angiogenesis or other cellular functions in order to restore sensitivity to irradiation. In this review, we focus on five classes of nucleic acid-based approaches, (i) gene transfer by recombinant plasmid or virus, (ii) immune-stimulating oligonucleotides, (iii) antisense oligonucleotides, (iv) siRNA and shRNA, and (v) siDNA (signal interfering DNA), which target specific proteins or pathways involved in radioresistance. We review the results of the preclinical studies and clinical trials conducted to date by combining nucleic acid-based molecular therapy and radiotherapy.

Effect of dynamic compression on in vitro chondrocyte metabolism.

BACKGROUND: Chondrocytes can detect and respond to the mechanical environment by altering their metabolism. This study was designed to explore the effects of dynamic compression on chondrocyte metabolism. METHODS: Chondrocytes were harvested from newborn Wistar rats. After 7 days of expansion, chondrocytes embedded in agarose discs underwent uniaxial unconfined dynamic compression loads at different amplitudes (5%, 10%, and 15%) and frequencies (0.5 Hz, 1.0 Hz, 2.0 Hz, and 3.0 Hz) with a duration of 24 hours. The delayed effects on the chondrocytes were studied at 1, 3, and 7 days after the experiment. RESULTS: The results showed that at 10% strain, higher-frequency compression pressure can enhance the proliferation of chondrocytes. The synthesis of glycosaminoglycan (GAG) increased at 10%-15% strain and a 1-Hz load. The synthesis of nitric oxide (NO) increased at the 0.5-Hz load; while decreasing at the 15% strain. With 10% strain, 1 Hz dynamic compression, the proliferation of chondrocytes and GAG synthesis increased and persisted for 7 days, and NO synthesis decreased at the third and seventh days of culture. CONCLUSIONS: This study showed that chondrocytes respond metabolically to compressive loading, which is expected to modulate the growth and the resultant biomechanical properties of these tissue-engineered constructs during culture.

Optimization of beta-carotene production by Rhodotorula glutinis using high hydrostatic pressure and response surface methodology.

Rhodotorula glutinis RG6 was treated by high hydrostatic pressure (HHP) of 300 MPa for 15 min for improving its ability of beta-carotene production. After the treatments of 5 repeated cycles, the mutant strain RG6p was obtained, beta-carotene production of which reached 10.01 mg/L, increased by 57.89% compared with 6.34 mg/L from parent strain RG6. To optimize the medium for beta-carotene fermentation by mutant RG6p, a response surface methodology (RSM) approach was used in conjunction with a factorial design and a central composite design, and the maximum yield of beta-carotene (13.43 mg/L), an increase of 34.17% compared to the control, was obtained at a pH 6.7 with an optimum medium (40 mL/250 mL) of yeast extract (4.23 g/L), glucose (12.11 g/L), inoculum (30 mL/L), tomato extract (2.5 mL/L), peanut oil (0.5 mL/L), and (NH(4))(2)SO(4) (5 g/L).

Targeted gene correction with 5' acridine-oligonucleotide conjugates.

Single-stranded oligonucleotides (SSOs) mediate gene repair of punctual chromosomal mutations at a low frequency. We hypothesized that enhancement of DNA binding affinity of SSOs by intercalating agents may increase the number of corrected cells. Several biochemical modifications of SSOs were tested for their capability to correct a chromosomally integrated and mutated GFP reporter gene in human 293 cells. SSOs of 25 nucleotide length conjugated with acridine at their 5' end increased the efficiency of gene correction up to 10-fold compared to nonmodified SSOs. Acridine and psoralen conjugates were both evaluated, and acridine-modified SSOs were the most effective. Conjugation with acridine at the 3' end of the SSO inhibited gene correction, whereas flanking the SSO by acridine on both sides provided an intermediate level of correction. These results suggest that increasing the stability of hybridization between SSO and its target without hampering a 3' extension improves gene targeting, in agreement with the "annealing-integration" model of DNA repair.

The in vitro effects of dehydroepiandrosterone on chondrocyte metabolism.

OBJECTIVE: To investigate the in vitro effects of dehydroepiandrosterone (DHEA) on neonatal rat chondrocytes. DESIGN: Chondrocytes isolated from neonatal rat cartilage were cultured in three-dimensionally agarose beads and were treated with DHEA. METHODS: Primary culture of chondrocytes was harvested from newborn Wistar rats. The DHEA effects on chondrocyte activities were evaluated by analyzing chondrocyte proliferation, matrix protein synthesis, gene expressions of collagen, matrix metalloproteinase-1, -3 and -13 (MMP-1, -3 and -13), and cyclooxygenase-2 (COX-II), and protein synthesis of interleukin-6 (IL-6), prostaglandin E2 (PGE2) and tissue inhibitor of metalloproteinase-1 (TIMP-1). RESULTS: The DHEA treatment did affect chondrocyte proliferation and glycosaminoglycan (GAG) synthesis. DHEA suppressed the expression of MMP-1, -3 and -13 genes and PGE2 protein synthesis enhanced by lipopolysaccharide (LPS) while the COX-II and inducible nitric oxide synthase (iNOS) gene expressions were down-regulated by DHEA. CONCLUSIONS: Our study demonstrates that DHEA has an ability to modulate the imbalance between MMPs and PGE2 in the neonatal chondrocytes which suggest that it has a potential protective role against articular cartilage damage.

Do natural DNA triple-helical structures occur and function in vivo?

Formation of natural intramolecular triple-helical structures of DNA is still an intriguing research topic in view of the possible involvement of these structures in biological processes. The biochemical and biophysical properties of DNA triplex structures have been extensively studied, and experimental data show that H-DNA is likely to form in vivo and may regulate the expression of various genes. However, direct and unambiguous evidence of the possible biological roles of these structures is yet elusive. This review focuses on the basic facts that are in favor of, or against, the hypothesis of the presence and function of natural DNA triple-helical structures in vivo, and outlines the different methods and probes that have been used to support these facts.

A new method (GOREC) for directed mutagenesis and gene repair by homologous recombination.

Directed mutagenesis in mammalian cells has been the focus of intense research because of its promising application for gene correction and engineering. Both natural and modified oligonucleotides (ODN), RNA-DNA chimeric oligonucleotide (RDO) and small fragment DNA (SFHR), as well as vector DNA were used for promoting homologous replacement with varying success. It was recently shown that a triple helix-forming oligonucleotide (TFO) tethered to an oligonucleotide (donor DNA) can enhance mutagenesis by homologous recombination in cells. The basic idea is to accelerate homology search by oligonucleotide-directed triple helix formation in the vicinity of the target site for donor DNA. Here we describe a new method named GOREC (guided homologous recombination) which shares similar gene targeting, but has notable difference in the concept with the previous method. It is made of a homing device (TFO) and a donor DNA for effecting distinct functions. They are linked together by non-covalent or covalent interaction. This modular concept allows guidance of either an oligonucleotide (ODN, RDO) or a small DNA fragment to the target site for homologous replacement. Therefore, the triple helix site can be hundreds of base pairs away from the target site. An episomal assay for proof-of-principle study will be presented and discussed.

The deleterious effect of tetanic contraction on rabbit's triceps surae muscle during cyclic loading.

To elucidate the effect of nerve stimulation on the mechanical property of muscle-tendon unit, the triceps surae muscle of New Zealand White rabbit was tested with material testing machine. After anaesthesia, the triceps surae muscle-tendon unit of rabbit was tested with cyclic loading during nerve stimulation. The differences between initial and residual force disappeared in the presence of low amplitude and low frequency nerve stimulation. Loading energy applied to the muscle-tendon unit did not change, but the unloading energy increased and energy loss decreased significantly. However, the residual force appeared again at the tetanic stimulation; the loading energy, unloading energy and energy loss all increased significantly.

Viscoplasticity of rabbit skeletal muscle under dynamic cyclic loading.

To elucidate the strain effects of dynamic cyclic loading on the skeletal muscle-tendon unit, the muscle-tendon unit of New Zealand white rabbits were tested with different strains and strain rates under ketamine general anaesthesia. The results indicated that the dynamic responses of muscular tissues were both strain and strain-rate dependent with appreciably non-linear characteristic. The muscle-tendon unit behaved viscoelastically below 12% strain; but when stretching more than 16% strain it began to behave plastically. The loading energies and unloading energy are more dependent on strain than on strainrate. RELEVANCE: This study offers firm evidence that plasticity may be one of the important biomechanical properties of the skeletal muscle. The findings in this report imply that the expression of skeletal muscle mechanical behaviour may not be limited to phenomena represented by a composition of elastic and viscous elements. The elongation of skeletal muscle under sustained stretching might be explained by the plastic property. Elucidation of the existence of viscoplasticity in skeletal muscle gives a good reference point to determine the functional capabilities and limitation of muscular tissue.

Biomechanical properties of the triceps surae muscle after limb lengthening.

The hindlimb of New Zealand white rabbit was osteotomized and then slowly lengthened at a rate of 1 mm/day until a 2.0-cm gain in length was reached. The triceps surae muscle-tendon unit was then tested either with or without 2 months fixation for bony consolidation. After limb lengthening, the strain at peak load was decreased and the axial rigidity was increased significantly; but other biomechanical parameters such as peak load, maximal deformation at peak load, stiffness, and energy absorption before peak load did not show any significant difference. We conclude that healthy triceps surae muscle has a great potential to be lengthened despite the changes in intrinsic structural properties of the muscle. The change in the biomechanical properties occurred during the time of distraction and was not affected by the time of bony consolidation. RELEVANCE: As noted in this study, many biomechanical parameters of the triceps surae muscle were not affected after prolonged distraction. This fact suggested that the healthy muscle-tendon unit is not a main causative factor of joint contracture after limb lengthening. However, there were intrinsic changes in the structural properties of the triceps surae muscle. Equinus contracture after limb lengthening may be caused by the aggravated intrinsic structural changes of the injured or denervated scarred muscular tissue.