Effects In Clinical Studies Research Articles

Comparative study of clinical effects between oblique lumbar interbody fusion (OLIF) and lateral lumbar interbody fusion (LLIF) in the treatment of degenerative disc disease of the lumbar spine

Objective: To compare the clinical effects of oblique lumbar interbody fusion (OLIF) and lateral lumbar interbody fusion (LLIF) in the treatment of degenerative disc disease of the lumbar spine. Method: This was a retrospective study. The clinical data of 80 patients with lumbar disc degenerative disease who underwent surgery in Affiliated Hospital of Beihua University from May 2018 to May 2023 were selected. The patients were divided into LLIF group and OLIF group according to surgical methods. Compare the 36-Item Short-Form Health Survey(SF-36), Visual Analog Scale(VAS) scores, Oswesterly Disability Index(ODI), Japanese Orthopedic Association(JOA) scores, Cobb angle, and intervertebral height changes between two groups of patients pre- and posttreatment, and evaluate the differences in clinical efficacy and surgical complications. Result: Postsurgery, the SF-36 score, VAS score, ODI index, and JOA score of two groups were significantly better than presurgery(p<0.05); After three months of treatment, the improvement in OLIF group was better than LLIF group(p<0.05), while there was no statistically significant difference between the two groups at six months postsurgery(p>0.05). Six months postsurgery, the intervertebral space height and Cobb angle of the two groups were significantly improved compared to presurgery (p<0.05), but there was no significant difference between the groups(p>0.05). There was no difference in clinical efficacy and incidence between the two groups(p>0.05). Conclusion: LLIF and OLIF may be both safe and effective minimally invasive surgical methods for the treatment of degenerative disc disease of the lumbar spine. doi: https://doi.org/10.12669/pjms.40.10.9344 How to cite this: Wang Y, Song Y, Ma Y, Sun X, Wang H. Comparative study of clinical effects between oblique lumbar interbody fusion (OLIF) and lateral lumbar interbody fusion (LLIF) in the treatment of degenerative disc disease of the lumbar spine. Pak J Med Sci. 2024;40(10):2238-2242. doi: https://doi.org/10.12669/pjms.40.10.9344 This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Clinical Study of Photobiomodulation Effect at Postoperative Clefted Alveolar Ridge Bone Grafting.

This study aimed to evaluate photobiomodulation (PBM) adjunct effect on pain, swelling, and face temperature in individuals with oral cleft submitted to alveolar ridge bone grafting (ABG). The sample consisted of 46 patients with either incomplete or complete unilateral cleft lip and palate aged from 9 to 18 years, both sexes, who underwent ABG with chin donor area. Subjects were randomly divided into 3 groups: (1) Control (C): ABG (n=17); (2) PBM: ABG with PBM (n=14); (3) Simulated photobiomodulation (SPBM): ABG with SPBM (n=15). Aluminum Gallium Arsenide (GaAlAs) infrared laser was used at 808±10nm and power of 100mW±20%. GaAlAs infrared laser was applied on 14 points in the subject's face at 4J per point, at 2 times: Immediate postoperative period and 24 hours postoperative. The authors evaluated pain, swelling, and face temperature at 24 hours postoperative; at 7-day postoperative, the authors evaluated pain, medication use, and swelling decreasing perception. No statistically significant difference occurred between groups C, PBM, and SPBM. At 24 hours postoperative, pain values showed statistically significant difference (P=0.04) between group C and SPBM. PBM at the tested parameters did not reduce pain and swelling and did not significantly change face temperature of individuals submitted to ARBG.

Known and unknown hymecromone. A review

Hymecromone (4-MU) is a recognized agent currently used in clinical practice. Since 1960, hymecromone has been used in many countries as a choleretic and cholespasmolytic, a drug approved for use in humans with biliary tract disorders. The review presents both traditional European and Russian studies of the selective antispasmodic and choleretic properties of hymecromone, due to which hymecromone is the drug of choice for the treatment of biliary tract diseases, as well as new fundamental and clinical studies of numerous pleiotropic effects of 4-MU associated with inhibition of hyaluronic acid and many other properties of this exciting molecule. These include antibacterial, antiviral, and nonspecific anti-inflammatory effects. Positive results have been demonstrated in carbohydrate and lipid metabolism disorders, autoimmune diseases, as well as liver, heart, and kidney diseases. Numerous in vitro and in vivo studies have been presented in pancreatic, prostate, skin, esophagus, breast, liver, ovary, bone cancers, metastatic lesions, leukemia, autoimmune and inflammatory diseases. Hymecromone is indicated not only as a choleretic and cholespasmolytic but also as a choleseptic in cholangitis and chronic cholecystitis, including opisthorchiasis, which does not disagree with its label. Odecromone® (hymecromone, tablets 200 mg) is available on the Russian market; it replaced the originator drug and is its fully equivalent generic.

Exploring Valeriana species: Unraveling anticonvulsant potential through phytochemistry and pharmacology

Background and aims: The Valerianaceae comprises about 300 species of annual and perennial plants found worldwide. Several species are utilized for biological purposes, while others are consumed. The various Valeriana species have different therapeutic effects, including sleep aid, sedative and anxiolytic, and anticonvulsant effects. The study intends to review the phytochemistry, pharmacological activities, and molecular pathways of these plants to explore their potential as therapeutic options for seizures and epilepsy. Methods: Until 2023, all relevant information about Valeriana species was gathered from PubMed, Scopus, Web of Science, and Embase. Valerianaceae, Valeriana, valeric acid, and Valeriana officinalis, phytochemical composition, in vivo investigations, epilepsy, neuroprotective, anticonvulsant, GABA, seizure, and preclinical and clinical research were among the search terms utilized for this review. Results: Based on the results obtained from the studies conducted in this field, significant anticonvulsant effects of various compounds extracted from the Valeriana species have been observed in multiple animal models, including pentylenetetrazole (PTZ)- and maximal electroshock (MES)-induced seizures in mice, rats, and zebrafish. It has also been determined that the molecular and pharmacological mechanisms involved in these anti-epileptic effects are increasing the GABA pathway, inhibiting the NMDA receptor and adenosine pathways, and nitric oxide (NO) modulation. Moreover, these compounds synergize with clonazepam, diazepam, phenobarbital, and phenytoin. Conclusion: It is recommended to prepare proper drug forms and study its anticonvulsant effects in clinical studies.

Breast cancer treatment with coenzyme Q10 (CoQ10)

Coenzyme Q10 (CoQ10) was identified in the late 1950s, and its potential role in cancer therapy appeared in the early 1960s when decreasing CoQ10 levels were found in some cancer patients. Breast cancer is a serious global health issue, and novel treatments are being developed. Its treatment is being investigated. CoQ10 has shown immune-boosting effects in clinical studies, encouraging researchers to look into its possible influence on breast cancer. Several research have looked at the link between CoQ10 and breast Coenzyme Q10 (CoQ10) was identified in the late 1950s, and its potential role in cancer therapy appeared in the early 1960s when decreasing CoQ10 levels were found in some cancer patients. Breast cancer is a serious global health issue, and novel treatments are being developed. Its treatment is being investigated. CoQ10 has shown immune-boosting effects in clinical studies, encouraging researchers to look into its possible influence on breast cancer. Several research have looked at the link between CoQ10 and breast cancer, focusing on its biological effects such as cytochrome c release and subsequent radical production. CoQ10 supplementation is commonly used by cancer patients to alleviate a perceived CoQ10 deficit associated with treatment-related toxicity. Notably, evidence shows that CoQ10 may be connected to lower tocopherol levels increasing the risk of breast cancer. However, bigger sample sizes, longer follow-up periods, and a better knowledge of the physiological role of circulating CoQ10 are required for a thorough assessment of CoQ10's possible role in breast cancer etiology. Antibacterial medications, therapy-induced adverse effects, and oxidative stress all have an impact on chemotherapy-related problems. Although CoQ10 has shown potential as an alternative breast cancer treatment, it is crucial to highlight that existing standard therapies, such as chemotherapy, radiation therapy, and hormone therapy, are not without their limitations. and targeted therapies are all options. Remain the cornerstone of breast cancer care. Always seek the most current and trustworthy information about breast cancer therapy from medical specialists.

Astounding the anxiolytic and eudemonic potential of certain fruits

Anxiety is a state of mind with some fear that affects physical health by disrupting neurotransmission and hormonal control. Both diet (inadequate and unhealthy dietary patterns) and environment (social and financial factors) trigger its progression; therefore, diet is considered to have a significant involvement in its prevention or adjunct therapy. A unique nutrient profile and bioactive ingredients are seen in fruits to provide health outcomes beyond nutritive properties. The relaxing potential of such fruits is attributed to the functional nature and therapeutic ingredients i.e., catecholamines, myricetin, quercetin, betalains, etc. that enhance the efficiency of hormones, neurotransmitters, and metabolic pathways. This review presented certain fruits having positive associations with mental health and anxiety amelioration. Various types of research evidenced the anxiolytic effect of certain fruits through clinical trials. Among them, berries, opuntia, and black pepper also have shown anxiety-relieving effects in clinical studies by restoring antioxidant enzymes, hormonal modulations, and managing neurotransmitters. Citrus species are loaded with flavonoids which are involved in the expression of GABA (Gamma-Amino Butyric Acid) to calm the nervous system. Some other fruits also potentiate memory and cognition when taken in ample amounts owing to their secondary metabolites. Thus, the incorporation of such fruits into a regular diet has been found to have a significant impact on mental well-being and brain health.

Days Alive and Out of Hospital as an Outcome Measure in Patients Receiving Hyperacute Stroke Intervention.

Patient outcome after stroke is frequently assessed with clinical scales such as the modified Rankin Scale score (mRS). Days alive and out of hospital at 90 days (DAOH-90), which measures survival, time spent in hospital or rehabilitation settings, readmission and institutionalization, is an objective outcome measure that can be obtained from large administrative data sets without the need for patient contact. We aimed to assess the comparability of DAOH with mRS and its relationship with other prognostic variables after acute stroke reperfusion therapy. Consecutive patients with ischemic stroke treated with intravenous thrombolysis or endovascular thrombectomy were analyzed. DAOH-90 was calculated from a national minimum data set, a mandatory nationwide administrative database. mRS score at day 90 (mRS-90) was assessed with in-person or telephone interviews. The study included 1278 patients with ischemic stroke (714 male, median age 70 [59-79], median National Institutes of Health Stroke Scale score 14 [9-20]). Median DAOH-90 was 71 [29-84] and median mRS-90 score was 3 [2-5]. DAOH-90 was correlated with admission National Institutes of Health Stroke Scale score (Spearman rho -0.44, P<0.001) and Alberta Stroke Program Early CT [Computed Tomography] Score (Spearman rho 0.24, P<0.001). There was a strong association between mRS-90 and DAOH-90 (Spearman rho correlation -0.79, P<0.001). Area under receiver operating curve for predicting mRS score >0 was 0.86 (95% CI, 0.84-0.88), mRS score >1 was 0.88 (95% CI, 0.86-0.90) and mRS score >2 was 0.90 (95% CI, 0.89-0.92). In patients with stroke treated with reperfusion therapies, DAOH-90 shows reasonable comparability to the more established outcome measure of mRS-90. DAOH-90 can be readily obtained from administrative databases and therefore has the potential to be used in large-scale clinical trials and comparative effectiveness studies.

Nanocurcumin prevents memory impairment, hippocampal apoptosis, Akt and CaMKII-α signaling disruption in the central STZ model of Alzheimer’s disease in rat

The central route of streptozotocin (STZ) administration has been introduced as a rat model of sporadic Alzheimer’s disease (AD). Curcumin was suggested to possess possible neuroprotective effects, which may be profitable in AD. However, the low bioavailability of curcumin hinders its beneficial effects in clinical studies. Earlier studies suggested that a bovine serum albumin-based nanocurcumin, produces superior neuroprotective effects compared to natural curcumin. In the present study, the protective effect of nanocurcumin in rat model of central STZ induced memory impairment was assessed. In addition, due to the importance of the hippocampus in memory, the amounts of hippocampal active caspase-3, Akt, and CaMKII-α were evaluated. Adult male Wistar rats weighing 250–300 g were used. STZ (icv) was injected during days 1 and 3 (3 mg/kg in divided), and nanocurcumin or curcumin 50 mg/kg/oral gavage was administered daily during days 4–14. Morris water maze training was performed on days 15–17, and the retention memory test was achieved on the 18th day. Following memory assessment, the rats were sacrificed and the hippocampi were used to assess caspase-3 cleavage, Akt, and CaMKII-α signaling. The findings revealed that nanocurcumin ingestion (but not natural curcumin) in the dose of 50 mg/kg was capable to prevent the impairment of water maze learning and memory induced by central STZ. Molecular assessments indicated that STZ treatment increased the caspase-3 cleavage in the hippocampus while deactivating Akt and CaMKII-α. Nanocurcumin reduced caspase-3 cleavage to a non-significant level compared to control group and restored Akt and CaMKII-α within the hippocampus while natural curcumin exerted no significant effect. These findings might suggest that nanocurcumin can restore memory deficit, hippocampal apoptosis as well as Akt and CaMKII-α signaling disruption associated with brain insulin resistance.

Genetics and Pathophysiological Mechanisms of Lipoprotein(a)-Associated Cardiovascular Risk.

Elevated lipoprotein(a) is a genetically transmitted codominant trait that is an independent risk driver for cardiovascular disease. Lipoprotein(a) concentration is heavily influenced by genetic factors, including LPA kringle IV-2 domain size, single-nucleotide polymorphisms, and interleukin-1 genotypes. Apolipoprotein(a) is encoded by the LPA gene and contains 10 subtypes with a variable number of copies of kringle -2, resulting in >40 different apolipoprotein(a) isoform sizes. Genetic loci beyond LPA, such as APOE and APOH, have been shown to impact lipoprotein(a) levels. Lipoprotein(a) concentrations are generally 5% to 10% higher in women than men, and there is up to a 3-fold difference in median lipoprotein(a) concentrations between racial and ethnic populations. Nongenetic factors, including menopause, diet, and renal function, may also impact lipoprotein(a) concentration. Lipoprotein(a) levels are also influenced by inflammation since the LPA promoter contains an interleukin-6 response element; interleukin-6 released during the inflammatory response results in transient increases in plasma lipoprotein(a) levels. Screening can identify elevated lipoprotein(a) levels and facilitate intensive risk factor management. Several investigational, RNA-targeted agents have shown promising lipoprotein(a)-lowering effects in clinical studies, and large-scale lipoprotein(a) testing will be fundamental to identifying eligible patients should these agents become available. Lipoprotein(a) testing requires routine, nonfasting blood draws, making it convenient for patients. Herein, we discuss the genetic determinants of lipoprotein(a) levels, explore the pathophysiological mechanisms underlying the association between lipoprotein(a) and cardiovascular disease, and provide practical guidance for lipoprotein(a) testing.

Cost-effectiveness analysis of the pediatric 20-valent pneumococcal conjugate vaccine compared with lower-valent alternatives in Argentina

ObjectivesThe 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended for infants in Argentina’s national immunization program (NIP) in a 2 + 1 schedule since 2012. Licensure of the 15-valent vaccine (PCV15) is anticipated soon, and the 20-valent vaccine (PCV20) recently received regulatory approval. This cost-effectiveness analysis examined the public health and economic implications of transitioning from PCV13 to either PCV15 or PCV20 in Argentina’s pediatric NIP. MethodsA decision-analytic Markov model was used with a 10-year time horizon and a 3.0% annual discount rate for costs and benefits. Vaccine effectiveness estimates were derived from Argentinian surveillance data, PCV13 clinical effectiveness and impact studies, and PCV7 efficacy studies. Population, epidemiologic, and economic inputs were obtained from literature and Argentinian-specific data. The study adopted a healthcare system perspective; sensitivity and scenario analyses were conducted to assess input parameters and structural uncertainty. ResultsCompared with PCV13, PCV20 was estimated to avert an additional 7,378, 42,884, and 172,389 cases of invasive pneumococcal disease (IPD), all-cause pneumonia, and all-cause otitis media (OM), respectively, as well as 3,308 deaths, resulting in savings of United States Dollars (USD) 50,973,962 in direct medical costs. Compared with PCV15, PCV20 was also estimated to have greater benefit, averting an additional 6,140, 35,258, and 142,366 cases of IPD, pneumonia, and OM, respectively, as well as 2,624 deaths, resulting in savings of USD 37,697,868 in direct medical costs. PCV20 was associated with a higher quality-adjusted life year gain and a lower cost (i.e., dominance) versus both PCV13 and PCV15. Results remained robust in sensitivity analyses and scenario assessments. ConclusionOver a 10-year horizon, vaccination with PCV20 was expected to be the dominant, cost-saving strategy versus PCV13 and PCV15 in children in Argentina. Policymakers should consider the PCV20 vaccination strategy to achieve the greatest clinical and economic benefit compared with lower-valent options.

Artificial intelligence approaches for phenotyping heart failure in U.S. Veterans Health Administration electronic health record.

Heart failure (HF) is a clinical syndrome with no definitive diagnostic tests. HF registries are often based on manual reviews of medical records of hospitalized HF patients identified using International Classification of Diseases (ICD) codes. However, most HF patients are not hospitalized, and manual review of big electronic health record (EHR) data is not practical. The US Department of Veterans Affairs (VA) has the largest integrated healthcare system in the nation, and an estimated 1.5 million patients have ICD codes for HF (HF ICD-code universe) in their VA EHR. The objective of our study was to develop artificial intelligence (AI) models to phenotype HF in these patients. The model development cohort (n=20000: training, 16000; validation 2000; testing, 2000) included 10000 patients with HF and 10000 without HF who were matched by age, sex, race, inpatient/outpatient status, hospital, and encounter date (within 60days). HF status was ascertained by manual chart reviews in VA's External Peer Review Program for HF (EPRP-HF) and non-HF status was ascertained by the absence of ICD codes for HF in VA EHR. Two clinicians annotated 1000 random snippets with HF-related keywords and labelled 436 as HF, which was then used to train and test a natural language processing (NLP) model to classify HF (positive predictive value or PPV, 0.81; sensitivity, 0.77). A machine learning (ML) model using linear support vector machine architecture was trained and tested to classify HF using EPRP-HF as cases (PPV, 0.86; sensitivity, 0.86). From the 'HF ICD-code universe', we randomly selected 200 patients (gold standard cohort) and two clinicians manually adjudicated HF (gold standard HF) in 145 of those patients by chart reviews. We calculated NLP, ML, and NLP+ML scores and used weighted F scores to derive their optimal threshold values for HF classification, which resulted in PPVs of 0.83, 0.77, and 0.85 and sensitivities of 0.86, 0.88, and 0.83, respectively. HF patients classified by the NLP+ML model were characteristically and prognostically similar to those with gold standard HF. All three models performed better than ICD code approaches: one principal hospital discharge diagnosis code for HF (PPV, 0.97; sensitivity, 0.21) or two primary outpatient encounter diagnosis codes for HF (PPV, 0.88; sensitivity, 0.54). These findings suggest that NLP and ML models are efficient AI tools to phenotype HF in big EHR data to create contemporary HF registries for clinical studies of effectiveness, quality improvement, and hypothesis generation.

Cost-effectiveness of PCV20 to Prevent Pneumococcal Disease in the Pediatric Population: A German Societal Perspective Analysis.

Since 2009, a pneumococcal conjugate vaccine (PCV) covering 13 serotypes (PCV13) has been included by Germany's Standing Committee on Vaccinations for infants, resulting in major reductions in pneumococcal disease (PD). Higher-valent vaccines may further reduce PD burden. This cost-effectiveness analysis compared 20-valent PCV (PCV20) under a 3+1 schedule with 15-valent PCV (PCV15) and PCV13, both under 2+1 schedule, in Germany's pediatric population. A Markov model with annual cycles over a 10-year time horizon was adapted to simulate the clinical and economic impact of pediatric vaccination with PCV20 versus lower-valent PCVs in Germany. The model used PCV13 clinical effectiveness and impact studies as well as PCV7 efficacy studies for vaccine direct and indirect effect estimates. Epidemiologic, utility, and medical cost inputs were obtained from published sources. Benefits and costs were discounted at 3% from a German societal perspective. Outcomes included PD cases, deaths, costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). In the base case, PCV20 provided greater health benefits than PCV13, averting more cases of invasive pneumococcal disease (IPD; 15,301), hospitalized and non-hospitalized pneumonia (460,197 and 472,365, respectively), otitis media (531,634), and 59,265 deaths over 10 years. This resulted in 904,854 additional QALYs and a total cost saving of €2,393,263,611, making PCV20 a dominant strategy compared with PCV13. Compared to PCV15, PCV20 was estimated to avert an additional 11,334 IPD, 704,948 pneumonia, and 441,643 otitis media cases, as well as 41,596 deaths. PCV20 was associated with a higher QALY gain and lower cost (i.e., dominance) compared with PCV15. The robustness of the results was confirmed through scenario analyses as well as deterministic and probabilistic sensitivity analyses. PCV20 3+1 dominated both PCV13 2+1 and PCV15 2+1 over 10 years. Replacing lower-valent PCVs with PCV20 would result in greater clinical and economic benefits, given PCV20's broader serotype coverage.

LC-MS/MS methods for simultaneous determination of youkenafil and its metabolite M1 in human seminal plasma and plasma: Application to evaluate the acute effect of youkenafil on semen quality and its pharmacokinetics in human

Youkenafil is a novel Phosphodiesterase type 5 inhibitor used for treating erectile dysfunction. N-desethyl compound of youkenafil (M1) is its main active metabolite. In this study, two methods were developed and validated for the simultaneous determination of youkenafil and M1 by HPLC-MS/MS in human matrices including seminal plasma and plasma, in which the multiple reaction monitoring and electrospray ionization in positive mode were adopted, and the deuterated youkenafil (youkenafil-d5) was selected as the internal standard. The collected semen sample was kept at room temperature for approximately 30 min until fully liquefied. The volume of the liquefied semen was measured and then divided into two parts. One part was centrifuged to obtain the seminal plasma for the content detection of youkenafil and M1, while the other part was used for routine semen analysis. The chromatographic separation was accomplished with the column of Poroshell 120 EC-C18 (5 × 2.1 mm, 2.7 μm, Agilent). Protein precipitation with methanol was used for the pretreatment of seminal plasma and plasma. The intra-run and inter-run precisions were less than 6.4 % (relative standard deviation) and accuracies were all within −4.7 %–6.8 % (relative error) in both matrices. All other validated bioanalytical parameters were within the acceptance criteria set by the FDA. The methods were successfully applied to different clinical studies of youkenafil. In the clinical study of the acute effect of youkenafil on semen quality in healthy males, the content of youkenafil in seminal plasma was extremely low. Concentrations of youkenafil and M1 in seminal plasma were lower than those in plasma, at 20.7 % and 4.49 % of the plasma concentration, respectively. There was no significant acute effect of youkenafil on semen quality. In the pharmacokinetic study of youkenafil after single dose-escalation administration, the exposure to youkenafil and M1 was non-linear with the dose in the range of 100–400 mg.

Assessment of the effect of the SLC5A2 gene on eGFR: a Mendelian randomization study of drug targets for the nephroprotective effect of sodium-glucose cotransporter protein 2 inhibition.

Sodium-glucose cotransporter protein 2 (SGLT2) inhibitors have been shown to have renoprotective effects in clinical studies. For further validation in terms of genetic variation, drug-targeted Mendelian randomization (MR) was used to investigate the causal role of SGLT2 inhibition on eGFR effects. Genetic variants representing SGLT2 inhibition were selected as instrumental variables. Drug target Mendelian randomization analysis was used to investigate the relationship between SGLT2 inhibitors and eGFR. The IVW method was used as the primary analysis method. As a sensitivity analysis, GWAS pooled data from another CKDGen consortium was used to validate the findings. MR results showed that hemoglobin A1c (HbA1c) levels, regulated by the SLC5A2 gene, were negatively correlated with eGFR (IVW β -0.038, 95% CI -0.061 to -0.015, P = 0.001 for multi-ancestry populations; IVW β -0.053, 95% CI -0.077 to -0.028, P = 2.45E-05 for populations of European ancestry). This suggests that a 1-SD increase in HbA1c levels, regulated by the SLC5A2 gene, is associated with decreased eGFR. Mimicking pharmacological inhibition by lowering HbA1c per 1-SD unit through SGLT2 inhibition reduces the risk of eGFR decline, demonstrating a renoprotective effect of SGLT2 inhibitors. HbA1c, regulated by the SLC5A2 gene, was negatively correlated with eGFR in both validation datasets (IVW β -0.027, 95% CI -0.046 to -0.007, P=0.007 for multi-ancestry populations, and IVW β -0.031, 95% CI -0.050 to -0.011, P=0.002 for populations of European origin). The results of this study indicate that the SLC5A2 gene is causally associated with eGFR. Inhibition of SLC5A2 gene expression was linked to higher eGFR. The renoprotective mechanism of SGLT2 inhibitors was verified from the perspective of genetic variation.

Therapeutic Vaccines in Breast Cancer

Breast cancer (BC) is a major worldwide health issue, characterised by an increasing occurrence in both males and females. The classification of breast cancer subgroups is determined by variations in hormone receptor expression. Although traditional breast cancer therapies, including chemotherapy, surgery, and radiotherapy, have demonstrated effectiveness in the treatment of patients, they are frequently associated with significant adverse effects and recurrence. The emergence of therapeutic vaccines has become a promising option for the field of immunotherapy. These vaccines enhance the body’s immune system to identify and eliminate cancerous tumour cells. The current approach to vaccine therapy for breast cancer focuses on the targeting of two main categories of antigens: tumour associated antigens and tumour specific antigens. Excitingly, multiple vaccine strategies for breast cancer treatment have been employed, all of which have demonstrated promise and effectiveness in clinical studies. Currently, proposed vaccine types include peptide-based vaccines, whole tumour cell vaccines, DNA/RNA-based vaccines, dendritic cell vaccines, and viral-vector vaccines, etc. This review examined the present state of different types of vaccines in breast cancer therapy, including the therapeutic mechanism and the treatment outcomes.

CLINICAL STUDIES OF THE REPELLENT EFFICACY OF BARS® VETERINARY DRUGS &#x0D; IN THE FARMS OF THE ARARAT MARZ OF ARMENIA

Under conditions of maximum seasonal and daily activity of blood-sucking diptera insects of the Ararat region of the Republic of Armenia, the repellent effectiveness of Bars® veterinary drugs was studied. The experiments involved 26 clinically healthy dogs aged 1 to 10 years, of both sexes. As a result of clinical studies of the repellent effectiveness of veterinary drugs Bars ® insectoacaricidal spray and Bars ® insecticidal drops applied to dogs individually, once, during the prevention of bites of diptera flying insects, according to the presented doses, rules and application techniques, the drugs showed a high effectiveness of the repellent effect in the conditions of farms of the Ararat marz for 5 days. During the physical examination, no side effects were detected from the use of Bars® insecticide spray and Bars® insecticide drops.

The role of polyunsaturated fatty acids in the neurobiology of major depressive disorder and suicide risk.

Long-chain polyunsaturated fatty acids (LC-PUFAs) are obtained from diet or derived from essential shorter-chain fatty acids, and are crucial for brain development and functioning. Fundamentally, LC-PUFAs' neurobiological effects derive from their physicochemical characteristics, including length and double bond configuration, which differentiate LC-PUFA species and give rise to functional differences between n(omega)-3 and n-6 LC-PUFAs. LC-PUFA imbalances are implicated in psychiatric disorders, including major depression and suicide risk. Dietary intake and genetic variants in enzymes involved in biosynthesis of LC-PUFAs from shorter chain fatty acids influence LC-PUFA status. Domains impacted by LC-PUFAs include 1) cell signaling, 2) inflammation, and 3) bioenergetics. 1) As major constituents of lipid bilayers, LC-PUFAs are determinants of cell membrane properties of viscosity and order, affecting lipid rafts, which play a role in regulation of membrane-bound proteins involved in cell-cell signaling, including monoaminergic receptors and transporters. 2) The n-3:n-6 LC-PUFA balance profoundly influences inflammation. Generally, metabolic products of n-6 LC-PUFAs (eicosanoids) are pro-inflammatory, while those of n-3 LC-PUFAs (docosanoids) participate in the resolution of inflammation. Additionally, n-3 LC-PUFAs suppress microglial activation and the ensuing proinflammatory cascade. 3) N-3 LC-PUFAs in the inner mitochondrial membrane affect oxidative stress, suppressing production of and scavenging reactive oxygen species (ROS), with neuroprotective benefits. Until now, this wealth of knowledge about LC-PUFA biomechanisms has not been adequately tapped to develop translational studies of LC-PUFA clinical effects in humans. Future studies integrating neurobiological mechanisms with clinical outcomes may suggest ways to identify depressed individuals most likely to respond to n-3 LC-PUFA supplementation, and mechanistic research may generate new treatment strategies.

Buprenorphine-Naloxone Film Versus Tablets for Opioid Use Disorder

What Is the Issue?&#x0D; &#x0D; Medication for opioid use disorder is essential for reducing cravings, withdrawal symptoms, and facilitating recovery, with buprenorphine being preferred over methadone by health care providers and people with opioid use disorder due to its lower overdose risk and perceived lower side effect profile.&#x0D; In Canada, buprenorphine is available in various formulations, including buprenorphine-naloxone (BUP-NAL), commonly chosen for its safety benefits and convenience.&#x0D; Sublingual buprenorphine-naloxone films offer faster dissolution and potentially other benefits compared to sublingual tablets, evaluating their comparative clinical and cost-effectiveness is important as they become more widely available.&#x0D; &#x0D; What Did We Do?&#x0D; &#x0D; To inform decisions about the appropriate selection of BUP-NAL formulations for treating individuals with opioid use disorder, CADTH sought to identify and summarize literature comparing the clinical effectiveness and cost-effectiveness of sublingual BUP-NAL films versus tablets. We also attempted to identify evidence-based recommendations for the use of BUP-NAL film.&#x0D; A research information specialist conducted a literature search of the peer-reviewed and grey literature with a search strategy focused on sublingual BUP-NAL. The search was limited to English-language documents published since January 1, 2018. One reviewer screened articles for inclusion based on predefined criteria, critically appraised the included study, and narratively summarized the findings.&#x0D; &#x0D; What Did We Find?&#x0D; &#x0D; Sublingual BUP-NAL films may have lower abuse rates compared to sublingual BUP-NAL tablets among people who seek treatment at substance abuse treatment centres or who present needing medical advice or treatment for intentional misuse or abuse of potentially toxic substances, including opioids (1 study).&#x0D; We did not find any clinical effectiveness studies that assessed aspects related to drug ingestion, drug abuse cessation, treatment programs, health-related quality of life, mental health or safety of BUP-NAL films or tablets that met our criteria for this review.&#x0D; We did not find any studies on cost-effectiveness or evidence-based guidelines of sublingual BUP-NAL films or tablets that met our criteria for this review.&#x0D; &#x0D; What Does It Mean?&#x0D; &#x0D; Limited evidence from this review suggests that sublingual BUP-NAL films may lead to lower substance abuse rates compared to sublingual BUP-NAL tablets among people with OUD; however, we require more comprehensive research with rigorous methodological approaches to understand this topic better.&#x0D; Considering the low abuse potential for BUP-NAL film, decision-makers may wish to use this formulation in settings where the potential for substance abuse is high.&#x0D;

Brain functions of saffron and crocin: Case report and literature review

Saffron is known to contain approximately 150 components, among which crocetin glycosides, i.e. crocin, safranal and picrocrocin have been found to be the active substances. In recent years, research on the anticognition activity of saffron has been widely conducted, and it has become clear that the active ingredient is crocin. Crocin is a component of crocetin with four glucose bonds, but as crocetin is a diterpene linked by conjugated double bonds, it is sensitive to oxygen, heat and light, causing secondary changes and degradation. For this reason, quality control is essential for researches. In-vitro experiments have shown that crocin has antioxidant and anti-inflammatory-lowering effects, lowered ceramide levels, increased glutathione levels, lowered amyloid-β, increased acetylcholine and dopamine levels and increased long-term potentiation. In in-vivo experiments, crocin increased memory learning capacity and activated long-term potentiation. Crocin also induced sleep effects, particularly non-REM sleep. Saffron was also found to have sleep effects in clinical studies. Epidemiological studies revealed that these effects were linked to anti-cognitive effects, so saffron and crocin can be said to be indirectly effective against Alzheimer’s disease. The clinical trial of saffron extract ameliorated symptoms in Alzheimer’s patients. From these findings saffron and crocin can potentially be applied for treatment and prevention of dementia in patients.

Zasługi Karola Linneusza dla postępu nauk farmaceutycznych w XVIII w.

The importance of Linnaeus’ taxonomy for the progress of pharmaceutical science in the 18th century Fundamentals of Linnaean taxonomy were established from the late 1730s and had a gradual ordering impact on all plant knowledge of the time. Pharmaceutical botany was enlivened by the following assertions, ideas or publications issued by Linnaeus: 1) the sexual system as a tool for practical identifi cation of genera; 2) the genera were newly defi ned or corrected to build a clear system; 3) botanists were encouraged to construct and study a natural system of genera which was expected to reveal similarities in pharmacological actions (as analogous to morphological similarities of allied species); 4) a critical and minimalist review of medicinal species and their therapeutical uses was published; 5) the synonymy of species was rectifi ed by selecting only good and suffi ciently descriptive polynomials; and fi nally 6) it became the new scientifi c standard to typify the name and description of a species on a proof sample, the role of which began to be played by a herbarium specimen of a plant, called a type. The practice of assigning binominal names to known or newly described species enabled botanists to place them immediately in the sexual system (by assigning a generic name, the genus was ranked in terms of fl ower structure). The increase in the number of medicinal plant species at the end of the 18th century was the result of a desire to make the knowledge complete and modern, and to add new facts about related species in a wellorganized form. Canons for the experimental and clinical study of effects of known and new medicinal plants on healthy and sick patients were being developed. The introduction of many new species into practical therapy took pharmacy by surprise, as the pharmacist had to learn to recognise medicinal plants previously unknown to pharmacy, which was not without its mistakes. Misrecognised plants that became drug ingredients could exert unintended effects in therapy, undermining the authority of physicians, hindering the evaluation of drugs and threatening to fl ood scientifi c pharmacy with a stream of erroneous knowledge. Continued practical self-education of pharmacists in the fi eld of plant taxonomy was therefore claimed.