The role of acute rehabilitation in COVID-19 patients.

BACKGROUND: In the published literature there is scarce data on the importance of acute rehabilitation in patients suffering from COVID-19 disease. AIM: Evaluation of the feasibility of respiratory and neuromuscular rehabilitation treatment in stable acute COVID-19 inpatients. DESIGN: The study was designed as an observational prospective investigation of two cohorts respectively identified as Mild/Moderate and Stable Severe COVID-19 disease. All patients received a rehabilitation treatment consisting of breathing exercises, range of motion exercises and strengthening exercises, with the main difference in intensity and progression of treatment, depending on individual capacity of patient. SETTING: Inpatients with diagnosed mild to moderate, or stable severe COVID-19 infection were included in the study. POPULATION: Acute COVID-19 inpatients. METHODS: Patients were divided into two groups depending on the severity of disease: "mild to moderate group" (MMG) and "stable severe group" (SSG). Functional outcomes included the Barthel Index (BI), Six Minute Walk Test (6MWT), Borg Scale for dyspnea, "Time Up and Go" Test (TUG), "Sit To Stand" test (STS), "One Leg Stance Test" (OLST) and Beck Depression Inventory (BDI) were evaluated at baseline and after rehabilitative treatment, on discharge. RESULTS: We included 147 acute COVID-19 inpatients (75 male and 72 female), mean aged 63.90±13.76 years. There were noticeable statistically significant improvements in all observed measurements in both groups. Comparison between groups showed significant difference in MMG compared to SSG in all functional outcomes: TUG (P<0.001), STS (P<0.001), OLST (P<0.001), BDI (P=0.008), BI (P<0.001), and Borg scale for dyspnea (P<0.001). Despite the significant improvements of BI in SSG, the obtained values showed that the patients were still not functionally independent. CONCLUSIONS: Acute respiratory and neuromuscular rehabilitation program is a feasibile, but also effective and safe method for improving functional status in patients with COVID-19 infection. CLINICAL REHABILITATION IMPACT: Results of the present study implicate that a supervised early rehabilitation program, implemented in the treatment of patients with COVID-19 disease in the acute phasis a feasible way for significant improvement of patient's functional outcomes. Early rehabilitation should be included into clinical protocols for the treatment of patients with COVID-19.

A 12-week exercise program improves functional status in postmenopausal osteoporotic women: randomized controlled study.

BACKGROUND: Beside the importance of implementing physical activity in treatment of patients with osteoporosis, the multicomponent exercise program and assessment of its functional outcomes performed by five performance-based measures, have not been explored yet. AIM: The present study evaluated the effect of the 12 weeks exercise program on functional outcomes of postmenopausal patients with densitometric diagnosed osteoporosis. DESIGN: The study was designed as randomized control study. SETTING: Female outpatients with diagnosed postmenopausal osteoporosis were included in the study. POPULATION: The study included women from urban area. METHODS: Patients were randomized in two groups: exercise group (EG) and control group (CG). Patients in the exercise group (N.=47) participated in a 12 weeks exercise program, which consisted of resistance training, balance exercise and aerobic exercise, while patients from control group (N.=49) had not participated in any exercise program during the intervention period. Functional outcomes determined by Time Up and Go Test (TUG), Sit To Stand test (STS) and One Leg Stance Test (OLST) were evaluated at baseline and 4 and 12 weeks after treatment, while Fall Efficacy Scale (FES-I) and Knowledge About Osteoporosis Questionnaire (OKAT-S) were assessed at baseline and after 12 weeks, respectively. RESULTS: There were noticed statistically significant improvement in all observed measurements in EG after 4 and 12 weeks, respectively. Comparison between groups showed statistically significant difference in EG compared to CG in all functional outcomes in observed periods (P<0.001 for all). OLST significantly changed only in EG, not in CG, in both experimental periods. After 4 weeks, in CG there were no statistically significant changes in any of the monitored parameters, while after 12 weeks improvements were detected with TUG, STS, FES-I and OKAT-S. CONCLUSIONS: Twelve weeks exercise program, as an effective, inexpensive and easily performed method, improved functional status in postmenopausal osteoporotic women. CLINICAL REHABILITATION IMPACT: In the present study we found that supervised exercise program in postmenopausal osteoporotic female patients significantly improved their muscle strength and balance and decreased fear of falling. Thus, it is proposed to be a part of clinical protocol for osteoporosis treatment.

Effects of 12-Week Exercise Program on Enzyme Activity of Serum Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 in Female Patients with Postmenopausal Osteoporosis: A Randomized Control Study.

BACKGROUND: Osteoporosis is a disease characterized by decreased bone density and destruction of bone microarchitecture. Indicators for altered bone homeostasis are changes in the serum level of matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs). The purpose of the current study was to evaluate the effect of a 12-week exercise program on enzyme activity of serum MMP-9 and TIMP-1 in postmenopausal osteoporotic patients. Materials and methods. Participants were randomized in two groups: exercise (EG) (N = 37) and control (CG) (N = 37) and control (CG) (. RESULTS: Significant differences between pretreatment and posttreatment enzyme activities of serum MMP-9 (p=0.009), TIMP-1 (p=0.009), TIMP-1 (p=0.009), TIMP-1 (. CONCLUSION: Our results suggest that a 12-week exercise program has an influence on enzyme activity of serum MMP-9, revealing a possible role of MMPs in initiating training-specific adaptation. Although measurements of circulating MMP-9 and TIMP-1 allowed us to detect effects of exercise, as of today, they have no real role in the diagnosis of osteoporosis and/or follow-up of osteoporotic patient's response to treatment. MMP-9 might be used as an important prognostic marker for the evaluation of patient's response to exercise. Larger-randomized controlled studies need to be performed to expand this area of knowledge. This trial is registered with trial registration number: NCT03816449).

Draft Genome Sequence of the Probiotic Yeast Kluyveromyces marxianus fragilis B0399.

Here, we report the draft genome sequence of Kluyveromyces marxianus fragilis B0399, the first yeast approved as a probiotic for human consumption not belonging to the genus Saccharomyces The genome is composed of 8 chromosomes, with a total size of 11.44 Mb, including mitochondrial DNA.

Capsid protein expression and adeno-associated virus like particles assembly in Saccharomyces cerevisiae.

BACKGROUND: The budding yeast Saccharomyces cerevisiae supports replication of many different RNA or DNA viruses (e.g. Tombusviruses or Papillomaviruses) and has provided means for up-scalable, cost- and time-effective production of various virus-like particles (e.g. Human Parvovirus B19 or Rotavirus). We have recently demonstrated that S. cerevisiae can form single stranded DNA AAV2 genomes starting from a circular plasmid. In this work, we have investigated the possibility to assemble AAV capsids in yeast. RESULTS: To do this, at least two out of three AAV structural proteins, VP1 and VP3, have to be simultaneously expressed in yeast cells and their intracellular stoichiometry has to resemble the one found in the particles derived from mammalian or insect cells. This was achieved by stable co-transformation of yeast cells with two plasmids, one expressing VP3 from its natural p40 promoter and the other one primarily expressing VP1 from a modified AAV2 Cap gene under the control of the inducible yeast promoter Gal1. Among various induction strategies we tested, the best one to yield the appropriate VP1:VP3 ratio was 4.5 hour induction in the medium containing 0.5% glucose and 5% galactose. Following such induction, AAV virus like particles (VLPs) were isolated from yeast by two step ultracentrifugation procedure. The transmission electron microscopy analysis revealed that their morphology is similar to the empty capsids produced in human cells. CONCLUSIONS: Taken together, the results show for the first time that yeast can be used to assemble AAV capsid and, therefore, as a genetic system to identify novel cellular factors involved in AAV biology.

Formation of AAV single stranded DNA genome from a circular plasmid in Saccharomyces cerevisiae.

Adeno-associated virus (AAV)-based vectors are promising tools for targeted transfer in gene therapy studies. Many efforts have been accomplished to improve production and purification methods. We thought to develop a simple eukaryotic system allowing AAV replication which could provide an excellent opportunity for studying AAV biology and, more importantly, for AAV vector production. It has been shown that yeast Saccharomyces cerevisiae is able to replicate and form the capsid of many viruses. We investigated the ability of the yeast Saccharomyces cerevisiae to carry out the replication of a recombinant AAV (rAAV). When a plasmid containing a rAAV genome in which the cap gene was replaced with the S. cerevisiae URA3 gene, was co-transformed in yeast with a plasmid expressing Rep68, a significant number of URA3(+) clones were scored (more than 30-fold over controls). Molecular analysis of low molecular weight DNA by Southern blotting revealed that single stranded DNA is formed and that the plasmid is entirely replicated. The ssDNA contains the ITRs, URA3 gene and also vector sequences suggesting the presence of two distinct molecules. Its formation was dependent on Rep68 expression and ITR. These data indicate that DNA is not obtained by the canonical AAV replication pathway.