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Network pharmacology analysis and clinical efficacy of the traditional Chinese medicine Bu-Shen-Jian-Pi. Part 3: Alleviation of hypoxia, muscle-wasting, and modulation of redox functions in amyotrophic lateral sclerosis

Int J Clin Pharmacol Ther. 2024 Mar 3. doi: 10.5414/CP204520. Online ahead of print.

ABSTRACT

OBJECTIVE: The aim of this clinical study is to obtain evidence for the clinical efficacy of Bu-Shen-Jian-Pi formula (BSJP), a traditional Chinese medicine, used for the treatment of amyotrophic lateral sclerosis, a relatively rare, progressive and usually fatal disease possibly associated with alterations in tissue redox status, hypoxia, and muscular injury.

BACKGROUND: The active agents in BSJP formula† causing apoptosis, modulation of redox changes, and alterations in the immune status have been studied previously by us using cell cultures. The findings from these investigations have been incorporated into pharmacology databases employed in our analysis of BSJP using network pharmacology analysis/artifical intelligence. This information has been used here in the design of the investigation and to optimize evaluation of the clinical efficacy and usefulness of this herbal medicine, as far as possible using evidence-based medicine criteria.

MATERIALS AND METHODS: The design of the study was a randomized multi-center, controlled clinical trial in 127 patients with confirmed diagnoses of amyotrophic lateral sclerosis. Patients and investigator were double-blinded. Clinical efficacy was determined using the Amyotrophic Lateral Sclerosis Symptom Score in Integrative Treatment Scale (ALS-SSIT) and the Amyotrophic Lateral Sclerosis Rating Scale-Revised (ALSFRS-R), together with tests of limb muscle strength using the manual muscle test (MMT), forced vital capacity (FVC), and clinical chemistry laboratory tests over a 20-week observation period.

RESULTS: The scores of ALS-SSIT in the BSJP group increased significantly (22%) after treatment. The ALSFRS-R score in the BSJP group decreased significantly after treatment (19%). The rate of decrease in muscle function (MMT score) in most BSJP patients was lower than that in the control group, where the differences in the scores for the trapezius and triceps brachii were statistically significant compared to the control group. The fall in FVC in the BJSP group was significantly slower than in the control group. There were no marked differences observed in the frequency of side effects. Serum vitamin D3 levels in the BSJP group showed greater increases compared to the control group.

CONCLUSION: BSJP treatment reduced the rate of progression of amyotrophic lateral sclerosis according to the ALS-SSITS and ALSFRS scores and significantly reduced the rate of deterioration in muscle function in the limbs of amyotrophic lateral sclerosis patients. The modes of action of BSJP in treating amyotrophic lateral sclerosis are probably diverse and multi targeted, some of which may involve regulation of serum vitamin D3 and alleviation of the impairments in liver and kidney function.

PMID:38431830 | DOI:10.5414/CP204520

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Determinants of non-diabetic kidney diseases in type 2 diabetic patients: Twenty years of single center experience

Clin Nephrol. 2024 Mar 3. doi: 10.5414/CN111093. Online ahead of print.

ABSTRACT

BACKGROUND: Diabetic nephropathy is one of the most common complications associated with diabetes. However, non-diabetic kidney disease has been reported in patients with type 2 diabetes at varying incidence rates. The objective of our study is to investigate the occurrence, clinicopathological characteristics, and inflammatory markers linked to diabetic and non-diabetic nephropathy (NDN) in patients with type 2 diabetes mellitus (DM). Additionally, we aimed to explore the possibility of identifying non-diabetic pathology using different biopsy indications.

MATERIALS AND METHODS: A total of 159 patients with type 2 DM who underwent renal biopsy at a tertiary care nephrology clinic between January 2000 and January 2022 were enrolled in the study. We collected comprehensive data, including patient demographics, co-morbidities, diabetes duration, renal biopsy indications and results, serological markers, renal function, diabetic retinopathy (DRP), full blood count, blood biochemistry, urinalysis, and inflammatory markers. Patients were categorized based on their biopsy indications, and their biopsy results were classified into three groups: isolated NDN, isolated diabetic nephropathy (DN), and mixed nephropathy with concurrent NDN. We evaluated the relationship between biopsy indications and accompanying pathologies and statistically assessed the likelihood of each biopsy indication detecting non-diabetic renal pathology. Additionally, differences in other data, including demographic and laboratory results and medical histories, among the three groups were investigated.

RESULTS: The most frequent indication of renal biopsy was atypical presentations of nephrotic syndrome or nephrotic range proteinuria (ANS/ANP) in 25.1% of patients. Other indications included unexplained renal failure (URF) in 22.6%, atypical presentations of non-nephrotic range proteinuria (ANNP) in 18.2%, acute kidney injury or rapidly progressive kidney dysfunction (AKI/RPKD) in 16.9%, microscopic hematuria in 15.7%, URF with ANNP in 11.3%, and severe nephrotic range proteinuria (SNP) in 9.4%. Renal biopsy revealed isolated NDN in 64.8%, DN in 25.1%, and mixed nephropathy in 10.1% of patients. Primary glomerular diseases were the main non-diabetic renal pathology, predominantly focal segmental glomerulosclerosis (FSGS) (36.4%) followed by MN (10.6%) and IgA nephropathy (7.5%). In comparison with the isolated DN and mixed nephropathy groups, patients in the isolated NDN group had significantly shorter diabetes duration, fewer DRP, as well as lower serum creatinine and neutrophil-to-lymphocyte ratio (NLR). Multivariate logistic regression analysis revealed that presence of hematuria (OR 4.40; 95% CI 1.34 – 14.46, p = 0.014), acute nephrotic range proteinuria (OR 11.93; 95% CI 1.56 – 90.77, p = 0.017), and AKI/APKD (OR 41.08; 95% CI 3.40 – 495.39, p = 0.003) were strong predictors of NDN. Lower NLR (OR 0.77; 95% CI 0.60 – 0.98, p = 0.035), shorter duration of diabetes (OR 0.90; 95% CI 0.84 – 0.97, p = 0.010), and absence of DRP (OR 0.35; 95% CI 0.12 – 0.98, p = 0.046) were also found to be independent indicators of NDN. Receiver operating characteristic curve (ROC) analysis revealed a cut-off value of ≤ 3.01 for NLR (sensitivity of 63.1%, specificity of 63.5%) with regards to predicting non-diabetic renal pathology (p = 0.006).

CONCLUSION: Renal biopsy findings in patients with type 2 DM highlight that the prevalence of NDN may be higher than assumed, as presented mainly in the form of primary glomerular disease. The presence of AKI/RPKD, hematuria, and ANS/ANP serves as a reliable indicator of non-diabetic renal pathology. In more ambiguous situations, factors such as a shorter duration of diabetes, absence of DRP, and a lower NLR value may assist clinicians in biopsy decision.

PMID:38431824 | DOI:10.5414/CN111093

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The impact of mitochondrial dysfunction on the pathogenesis of atherosclerosis

Wiad Lek. 2024;77(1):153-159. doi: 10.36740/WLek202401119.

ABSTRACT

OBJECTIVE: Aim: To determine the role of mitochondrial dysfunction in the pathogenesis of atherosclerosis based on the analysis of research data and statistics from the MEDLINE, Scopus and Web of Science Core Collection electronic databases for 2007-2023.

PATIENTS AND METHODS: Materials and Methods: A comprehensive review of literature sources from the MEDLINE, Scopus and Web of Science Core Collection electronic databases was conducted to critically analyse the data and determine the role of mitochondrial dysfunction in the pathogenesis of atherosclerosis.

CONCLUSION: Conclusions: In this review, we have summarized the latest literature data on the association between mitochondrial dysfunction and the development of atherosclerosis. Mitochondria have been recognized as a novel therapeutic target in the development of atherosclerosis. However, the presence of current gaps in therapeutic strategies for mitochondrial dysfunction control still hinders clinical success in the prevention and treatment of atherosclerosis. Both antioxidants and gene therapy are appealing approaches to treating atherosclerosis. Nevertheless, further research is needed to determine the proper therapeutic strategy to reduce the impact of mitochondrial dysfunction on the progression of atherosclerosis.

PMID:38431820 | DOI:10.36740/WLek202401119

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COVID-19 associated anosmia in pediatric patients: subject publications review

Wiad Lek. 2024;77(1):114-119. doi: 10.36740/WLek202401114.

ABSTRACT

OBJECTIVE: Aim: To review the publications subject to the problem of COVID-19 associated anosmia incidence in pediatric patients as well as its pathogenesis, diagnostics, treatment and recovery. The peculiarity of pediatric COVID-19 anosmia is due to children accounting for very low percentage of COVID-19 patients (comparing to one in adults), mostly with milder course of the disease. Awareness of anosmia and its proper diagnostics is crucial in children and adolescents, considering it can be the only manifestation in COVID-19 positive pediatric patients.

PATIENTS AND METHODS: Materials and Methods: In order to achieve this goal a meta-analysis of information from databases followed by statistical processing and generalisation of the obtained data was carried out.

CONCLUSION: Conclusions: Publications on COVID-19 anosmia in children and adolescents are less numerous than those concerning adult patients, so it is important to use every single trustworthy one. Anosmia/ageusia may be the only symptom, early identifier and the strongest predictor of COVID-19 infection in pediatric patients. Prospects for further scientific researches. Further researches regarding differential diagnostics of COVID-19 and other infections, including seasonal influenza, manifesting with both olfactory and taste dysfunction as well as anosmia diagnostics in children and adolescents with autistic spectrum and different types of mental disorders are possible.

PMID:38431815 | DOI:10.36740/WLek202401114

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Public management of public healthcare under the COVID-19 outbreak: experience of Ukraine

Wiad Lek. 2024;77(1):94-104. doi: 10.36740/WLek202401112.

ABSTRACT

OBJECTIVE: Aim: The research is aimed to study certain aspects and experience of functioning of the Ukrainian Public Healthcare public management mechanisms during an outbreak of the acute respiratory disease COVID19.

PATIENTS AND METHODS: Materials and Methods: The studied materials include personal observations and accumulated practical material, as well as generalization of the collected data and their empirical treatment, conducted by the scientists, according to the present legislation requirements. The study was held using general scientific methods, including observation, description of results, specification and statistical data generalization.

CONCLUSION: Conclusions: Generalization, arrangement and analysis of the Ukrainian experience of the Public Healthcare public management during the outbreak of the acute respiratory disease COVID19, provides exchange of experience between all subjects of the process. This helps to produce certain practical decisions, aimed at effective responding of the state healthcare system onto management of the COVID19 outbreak. Such activities are also directed at detection of flaws in the whole system, with their subsequent correction, and elimination or neutralization of possible negative outcomes. To adopt the priority activity directions within public relations, which make the subject of the study, the authors have studied a complex of activities against spread of the COVID19 in 2019-2020. These activities include issues, related to prompt responding onto the infection spread and approving quick professional decisions; fulfilling epidemiological supervision and introducing anti-epidemic activities; providing diagnostics, and accessibility of the safe and high-quality vaccine.

PMID:38431813 | DOI:10.36740/WLek202401112

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Reparative osteogenesis in mandible in cases of filling a bone defect with hydroxyapatite-containing osteotropic material and injecting the surrounding soft tissues with thymalin: experimental and morphological study

Wiad Lek. 2024;77(1):68-76. doi: 10.36740/WLek202401110.

ABSTRACT

OBJECTIVE: Aim of the study was to identify the morphological features of reparative osteogenesis in the lower jaw bone of rats in cases of filling a bone defect with hydroxyapatite-containing osteotropic material (bone graft “Biomin GT”) and injecting the surrounding soft tissues with thymalin.

PATIENTS AND METHODS: Materials and Methods: An experiment was conducted on 48 mature rats of the WAG population weighing 160-180 grams which were divided into four groups. Group 1 included 12 rats with a simulated holey defect in the lower jaw. Group 2 included 12 rats with a simulated holey defect in the lower jaw followed by its closure with hydroxyapatite-containing osteotropic material (bone graft “Biomin GT”). Group 3 included 12 rats with a simulated holey defect in the lower jaw with injecting the surrounding soft tissues with thymalin. Group 4 included 12 rats with a simulated holey defect in the lower jaw followed by its closure with hydroxyapatite-containing osteotropic material (bone graft “Biomin GT”) and injecting the surrounding soft tissues with thymalin. The material for the morphological study was a fragment of the lower jaw from the area of the simulated holey defect. Histological, morphometric and statistical research methods were used.

RESULTS: Results: In this study, it was shown by the authors an activation of reparative osteogenesis in the lower jaw under conditions of simultaneous filling the bone defect with hydroxyapatite-containing osteotropic material (bone graft “Biomin GT”) and injection the surrounding bone defect soft tissue with thymalin. Stimulation of reparative osteogenesis in the lower jaw of rats occurred due to rapid cleaning of the bone defect cavity from necrotic tissues and hematoma fragments; a decrease in the number of neutrophil leukocytes, an increase in the number and morphofunctional state of monocytes, macrophages, lymphocytes, cells of fibroblastic differon; balanced change (increase or decrease) in the number and morphofunctional state of bone forming osteoblasts and bone resorbing osteoclasts depending on the stage of reparative osteogenesis; activation of hematopoietic processes in lamellar bone tissue from the regenerate; activation of bone tissue mineralization processes.

CONCLUSION: Conclusions: Thymalin injection in the soft tissues surrounding the bone defect in the lower jaw, filled with hydroxyapatite-containing osteotropic material (bone graft “Biomin GT”), significantly stimulates the process of reparative osteogenesis, which makes it possible to recommend this technique in dentistry for treatment the patients with mandible bone tissue defects.

PMID:38431810 | DOI:10.36740/WLek202401110

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International classification of functioning, disability and health with long-term consequences of cranio-brain injury

Wiad Lek. 2024;77(1):29-34. doi: 10.36740/WLek202401104.

ABSTRACT

OBJECTIVE: Aim: To describe health status and related functioning of patients with different severity of traumatic brain injury (TBI) in past medical history in Ukraine and determining the feasibility of using the International Classification of Functioning, Disability and Health (ICF) Brief Core Set for TBI.

PATIENTS AND METHODS: Materials and Methods: A total of 102 patients, who were treated in the neurological department of Dnipropetrovsk regional clinical hospital and State Institution ≪Ukrainian State Scientific Research Institute of Medical and Social Problems of Disability of Health Ministry of Ukraine≫, had been examined. Patients were divided into three groups: mild, moderate and severe TBI in past history and evaluated using ICF Brief Core Set for TBI.

RESULTS: Results: Тhe most common problems in the functioning and health of patients in remote period of TBI, along with the influencing factors have been identified in the study. The most frequent categories from ≪Body Functions≫ and ≪Activity and Participation≫ sections in which patients had alterations were: memory functions, emotional functions, sensation of pain, functions of attention, brain structure, complex interpersonal interactions, family relationships. The increase in the amount and severity of disturbances with increasing severity of TBI had been established in all categories, except complex interpersonal interactions and family relationships.

CONCLUSION: Conclusions: Patients of all groups identified the family and close relatives, healthcare service and social welfare services, as the most frequent relieving factors of life activity. The use of the ICF Brief Core Set for assessing the subjects with TBI in past history provides a convenient procedure to standardize and structure functioning description. Information collected by the ICF Brief Core Set may be used for different purposes: clinical assessment, administration of medical services, planning and implementation of rehabilitation and evaluation of results, in scientific research, reports and health care statistics.

PMID:38431804 | DOI:10.36740/WLek202401104

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Pregravid preparation of women with chronic endometritis in IVF cycles

Wiad Lek. 2024;77(1):25-28. doi: 10.36740/WLek202401103.

ABSTRACT

OBJECTIVE: Aim: of our study was to improve the pregravid preparation of women with chronic endometritis to develop individual approaches to overcoming infertility, taking into account the state of endometrium.

PATIENTS AND METHODS: Materials and Methods: The study included 90 women (main group, n=90), 28 to 38 years with an anatomically normal uterus and chronic endometritis (CE). Patients were divided into 2 groups: group I – 45 women with CE who received conventional treatment; group II – 45 women with CE who received pregravid preparation by subendometrial injections of Platelet-Rich Plasma (PRP).

RESULTS: Results: At the first stage of study, the ART statistical reports from 2015 to 2022 were analyzed at the Medical Center of Reproductive Health ≪Damia≫, (Ivano-Frankivsk). Analysis of the vaginal flora parameters before treatment at the first stage revealed the presence of conditionally pathogenic flora in culture from the cervical canal (Candida albicans – 2.4%, Escherihia coli – 4.8%, Staphylococcus epidermidis – 6.2% Enterococcus faecalis – 6.9%), and was evidence of a possible recurrence of inflammation during gestation. In the age category, the groups of patients were homogeneous, with no significant differences by the level of AMH and the level of CD 138. Biochemical pregnancy be present in 20 patients (44.4%) of group I and 28 (62.2%) of group II. Fertility within a year after the end of therapy was restored with the proposed method of therapy in most women (51.1%), in the comparison group this number was 11.1% lower. Pregnancy rate between the groups (I and II) did not differ significantly. The number of live births in group II – 19 births (42.2%) – was 2 times higher than I group (9 (20.0%), P<0.05). The most common complication for women in the comparison groups was early pregnancy loss. Among 18 (40.0%) clinical pregnancies of group I, 8 women (17.8%) had early miscarriage, 1 ectopic pregnancy (2.2%), while in group II clinical pregnancy be present in 23 women (51.1%). The number of terminated pregnancies was two times lower than in the first group (8.9% vs. 17.8%, P<0.05).

CONCLUSION: Conclusions: Chronic endometritis is one of the main causes of pregnancy loss after in vitro fertilization. Patients of the second group were treated with the proposed method of subendometrial injections with Platelet-Rich Plasma (PRP), prepared from autologous blood, is an effective method of preparing the endometrium for embryo transfer and can increase the number of live births in patients with chronic endometritis.

PMID:38431803 | DOI:10.36740/WLek202401103

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Rainbow phlebotomy collection and urine aliquots for emergency department add-on testing in the era of pandemic-driven supply shortages

Lab Med. 2024 Mar 2:lmae011. doi: 10.1093/labmed/lmae011. Online ahead of print.

ABSTRACT

BACKGROUND: Rainbow blood draws for add-on testing in the emergency department (ED) are a common practice at our institution. We sought to determine the prevalence of this practice among reference laboratory clients and characterize the impact of pandemic-driven supply shortages.

METHODS: This cross-sectional study surveyed 354 client laboratories to understand specimen collection practices in specific clinical environments and how these practices may have been affected by supply chain shortages. Data analysis by descriptive statistics was performed in Qualtrics.

RESULTS: A total of 138 laboratories took the survey (39% response rate) with 57% indicating that their ED performed rainbow draws. Of these, 16% have a formal policy regarding rainbow draws, and 76% of respondents indicated that their institution was required to modify practices due to pandemic-driven supply shortages. A total of 19% indicated they routinely collect multiple urine aliquots for add-on testing.

CONCLUSION: Rainbow draws and collection of urine aliquots in the ED for add-on testing are relatively common practices, with few institutions maintaining formal policies regarding the practice. Pandemic-driven supply chain shortages affected a majority of respondent laboratories and local cost-benefit analysis regarding extra specimen collection is recommended to limit waste of laboratory resources.

PMID:38431798 | DOI:10.1093/labmed/lmae011

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Attitudes toward research and scholarly activities among medical laboratory science professionals in the United States

Lab Med. 2024 Mar 2:lmad120. doi: 10.1093/labmed/lmad120. Online ahead of print.

ABSTRACT

BACKGROUND: Medical laboratory science (MLS) professionals play a crucial role in health care teams. However, research culture in the profession has not been well developed or studied. It is necessary to characterize attitudes toward research and scholarly activities among MLS professionals and identify ways to promote research in the profession.

METHODS: A cross-sectional survey was administered through American Society for Clinical Laboratory Science channels. Survey responses were summarized using descriptive statistics, and linear regression models were constructed to identify characteristics that predicted 2 research attitudes: “valuing the role of research” and “perceived research environment” in the profession.

RESULTS: Of the 116 MLS professionals in this study, 53% reported currently participating in research activities. Opinions toward research were generally positive, although many respondents were not currently conducting research. Individuals with education and research practice focuses tended to place greater value on research, and education level was a significant predictor of perceived research environment. Dedicated research time and mentorship were cited as effective ways for employers to promote research in MLS.

CONCLUSION: Overall, respondents had favorable attitudes toward research in MLS, but approximately half of participants noted a lack of incentives to conduct research. This study highlights several initiatives that may be effective for promoting increased research activity among MLS professionals.

PMID:38431783 | DOI:10.1093/labmed/lmad120