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Using the guidelines from the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA), this meta-analysis (MA) tried to figure out how well creatine (Cr) improves metabolic performance. We searched Google Scholar, PubMed, and the Cochrane Library to identify relevant randomized clinical trials (RCTs) exploring the various effects of Cr across different age groups compared to a placebo (PLA). We also investigated the synergistic effects of combining other supplements with Cr. In order to emphasize the different ways and sports where Cr has been used in the past years, we found from the selected articles that Cr demonstrated a more pronounced effect during aerobic or anaerobic exercise compared to PLA groups in the studies. Furthermore, in sports that demand significant cumulative energy, such as long-distance races, biking, or triathlons, athletes have observed performance enhancements with Cr supplementation. We also stipulate that Cr enhances resistance training in people over 50 years old and that adding other training supplements, such as ß-hydroxy ß-methylbutyrate (HMB), synergistically improves training outcomes when combined with Cr. The current MA was based on a thorough analysis of 10 separate studies. When these results were added together, we found that taking Cr supplements demonstrated statistically significant benefits over PLA. In conclusion, the present MA has found evidence that Cr has positive effects on metabolic outcomes for people who consume it.

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Urinary incontinence (UI) is a prevalent health concern in females over 60, but it is prevalent in a smaller percentage of males. The medical and social elements of UI are crucial. This disorder may cause embarrassment and low self-esteem, reducing social and physical activities. Consequently, this may impair healthy aging. Researchers have shown that pelvic floor muscle training (PFMT) may improve UI symptoms in middle-aged, older, and young people. Clinical practice highlights the importance of PFMT for UI due to its low cost-effectiveness. To assess PFMT's overall efficacy, we conducted a systematic review of the literature (SRL) and a meta-analysis (MA) of randomized clinical trials (RCTs). The previous 10 years of published material were combed using the online databases the Cochrane Library, PubMed, and Google Scholar. Eligible total studies were RCTs referring to the effectiveness of PFMT. The pooled incidence, risk ratio, and 95% confidence interval (CI) of the effectiveness of PFMT were calculated using the fixed effects model. Given the possibility of a between-study variance, we used the fixed effects model rather than the random effects model.

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It is expected that the prevalence of atrial fibrillation (AF), the most prevalent cardiac arrhythmia among people aged 65 to 85, would be mostly classified using the CHAS2DS2-VASc approach for anticoagulation therapy. A high number of people in the entire world will be living with AF by 2030. Long-term follow-up data are sparse, although radiofrequency catheter ablation (CA) for symptomatic AF patients has the potential to be a curative therapy. Although women are referred later and less often than men, the outcomes following ablation are comparable across both genders. Health-related quality of life suffers from AF, and patients often find themselves less active as a result of their condition. AF may have a wide variety of symptoms and signs from the clinic's point of view. Women are more likely to exhibit symptoms than men; one reason for this is that women have an average QT interval that is 10-20 milliseconds longer than men, which is more likely to exacerbate tachycardia symptoms. In search of medical databases for relevant medical literature, we looked at PubMed/Medline, the Cochrane Library, and Google Scholar. Ten publications were gathered after the papers were located, assessed, and qualifying criteria applied were used to select them. The finished articles were done to give an overview of the effectiveness of ablation therapy for AF. Some studies showed that there was no statistical significance between invasive and pharmacological treatments. Other research found no difference in the recurrence of atrial arrhythmia between pulmonary vein isolation (PVI) CA alone and PVI + enhancement magnetic resonance imaging (MRI)-guided fibrosis ablation in individuals with persistent AF. The oldest individuals in studies comparing CA to medical treatment for AF demonstrated no improvement in prognosis after CA. Also, complications from therapy and CA's efficacy in preventing future atrial arrhythmias were similarly low across all age groups. Based on the above, we concluded that more studies are required to establish the most effective approach to treating AF to apply it in daily practice and gain more knowledge about it.

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In this research, physical activity (PA) was shown to be inversely associated with the incidence of diabetes. This emphasizes the relevance of PA in diabetes prevention lifestyle intervention initiatives and encourages healthcare practitioners to advise high-risk patients on a healthy lifestyle combining PA for the reduction of weight in prediabetic, obese, and type 2 diabetes mellitus (T2DM) patients. The link between PA and diabetes was stronger in people with moderate or higher baseline PA, reflecting national recommendations that imply increasing activity levels may provide larger advantages for those who are comparatively less active. An intensive lifestyle intervention of eating healthier foods and increasing PA resulted in an effective decrease in weight and waist circumference after one year, which has high potential in the long term to prevent T2DM and different comorbidities such as obesity. Studies such as PRomotion Of Physical activity through structured Education with differing Levels of ongoing Support for those with prediabetes (PROPELS) demonstrate that the combination of PA interventions with telemedicine follow-ups results in ambulatory activity changes in the first year, but these changes do not last longer than four years. Acute PA practicing regularly will reduce postprandial glucose excursions. However, it is unknown what type of PA routine will benefit the most from reducing postprandial glucose levels. There are no discernible variations in the effects of different disciplines of training on glucose levels, mainly when the data are compared across time. The combination of a healthy diet and lifestyle with programs based on diabetes prevention results in comparable and clinically significant mean weight reduction with cardiometabolic advantages. Based on the reviewed and cited studies, PA in patients at high risk of T2DM and obese and non-obese patients with T2DM results in favorable outcomes in the first few months. There is a large gap in investigations of the effects of PA in these patients and the benefits of other lifestyle modifications in long-term-based studies. However, in this study, we emphasize the importance of lifestyle modifications, putting in perspective principally the PA that the majority of patients with comorbidities do not practice, especially those with obesity, prediabetes, and T2DM. Thus, it would be necessary to conduct long-interval studies such as randomized clinical trials, where a better outcome can be given about intervals based on daily exercise times and the type of exercise in conjunction with diets that will have the greatest benefit, focusing more on the subjects that our research mentioned.

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Multiple studies have shown that intermittent fasting (IF) is associated with better health conditions and longer lifespans, as is time-restricted feeding (TRF). One crucial explanation is that IF and TRF permit a set length of time for caloric ingestion, during which our systems activate a variety of mechanisms that lead to the enhancement and renewal of different body systems. Accordingly, the benefits of IF and TRF are a lot greater than those of complete calorie restriction (CR). Accordingly, TRF and IF offered the underpinnings for human studies that revealed that when we eat and when we are fasting, we experience fluctuations in all body systems. For relevant medical literature, we investigated medical databases such as PubMed/Medline, PubMed Central, Cochrane Library, and Google Scholar. The chosen articles were evaluated based on eligibility criteria and vetted by quality evaluation methods; 15 finished research papers were included in the study. Of the 15 recognized studies, four were systematic reviews of literature, and 11 were review articles. The chosen publications all examined the efficacy and comparability with other restrictive diets. The study articles indicated that the advantages of IF and TRF represent complex interplay involving periodic digestion of food, gut flora, and the circadian clock. Accordingly, further research is necessary to get a comprehensive grasp of this very complex molecular blueprint. This could aid in producing an effectively planned food treatment that can regulate numerous chronic health ailments and disorders. Furthermore, it might lead to the development and investigation of new pharmacological medicines that mimic the nutritional and therapeutic benefits of IF for those who are unwilling or unable to follow this kind of feeding regimen.

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IBD consists of two diseases-CD and UC-that affect the digestive tract, with a greater affinity for the large bowel. In this case report, we focus on one of its most common complications. CDI is a pathology that is mostly secondary to UC. Another cause of this bacterial infection is established after the use of antibiotics, most commonly at the hospital level. Around 20 percent of CDI persists because of a chronic dysbiosis of the microbiota and low levels of antibodies against CD toxins. In this case report, we demonstrated mdCDI in a young woman after treatment with multiple drug therapies as well as with semi-invasive procedures as follows: antibiotics (vancomycin, fidaxomicin), anti-inflammatory agents (mesalamine, sulfasalazine), corticosteroids (budesonide, prednisone), integrin receptor antagonists (vedolizumab), several semi-invasive procedures such as fecal transplant microbiota (FMT), aminosalicylates (5-ASA), treatment with tumor necrosis factor (TNF) blockers (adalimumab, golimumab), and immunomodulators (upadcitinib, tofacitinib). This leads us to establish how rCDI and its resistance to different treatments make this a challenge for the health system, both for hospitals and for outpatients, as well as how time-consuming each treatment is from the first intake of the drug until its total efficacy or until patients reach a dose-response and time-response to the disease. Accordingly, this case report and other similar cases reflect the need for randomized control trials or meta-analyses to establish therapeutic guidelines for cases of mdCDI in the near future.

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Intramolecular Diels-Alder vinylarene reaction (IMDAV) is a [4 + 2] cycloaddition that employs styrene derivatives as conjugated dienes, whose poor reactivity arises from the required loss of aromaticity, which is recovered by a subsequent [1,3]-H shift. Herein, we describe the use of cyclopropene as a dienophile, harnessing its strain energy to drive the IMDAV reaction. Benzonorcarane scaffolds form in good yields, excellent stereoselectivity, and broad functional tolerance. Theoretical calculations and NMR studies have revealed significant mechanistic insights.

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Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder that leads to various long-term complications. However, we are describing an association between this patient's condition and primary biliary cholangitis (PBC). A 55-year-old male patient presented to our clinic with PBC, demonstrating the importance of how PBC can be clinically asymptomatic and the importance of the criteria given to diagnose the disease. We encourage physicians to periodically check all ADPKD patients to guard against asymptomatic problems that might endanger their health in the future.

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Influenza virus infection remains a threat to human health since viral hemagglutinins are constantly drifting, escaping infection and vaccine-induced antibody responses. Viral hemagglutinins from different viruses display variability in glycan recognition. In this context, recent H3N2 viruses have specificity for α2,6 sialylated branched N-glycans with at least three N-acetyllactosamine units (tri-LacNAc). In this work, we combined glycan arrays and tissue binding analyses with nuclear magnetic resonance experiments to characterize the glycan specificity of a family of H1 variants, including the one responsible for the 2009 pandemic outbreak. We also analyzed one engineered H6N1 mutant to understand if the preference for tri-LacNAc motifs could be a general trend in human-type receptor-adapted viruses. In addition, we developed a new NMR approach to perform competition experiments between glycans with similar compositions and different lengths. Our results point out that pandemic H1 viruses differ from previous seasonal H1 viruses by a strict preference for a minimum of di-LacNAc structural motifs.

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High-fat diets enriched with lauric acid (SOLF) do not enhance leptin production despite expanding white adipose tissue (WAT). Our study aimed at identifying the influence of SOLF vs. oleic acid-enriched diets (UOLF) on the autoparacrine effect of leptin and was carried out on eight-week-old mice consuming control chow, UOLF or SOLF. Phosphorylation of kinases integral to leptin receptor (LepR) signalling pathways (705Tyr-STAT3, 473Ser-Akt, 172Thr-AMPK), adipocyte-size distribution, fatty acid content, and gene expression were analyzed in WAT. SOLF enhanced basal levels of phosphorylated proteins but reduced the ability of leptin to enhance kinase phosphorylation. In contrast, UOLF failed to increase basal levels of phosphorylated proteins and did not modify the effect of leptin. Both SOLF and UOLF similarly affected adipocyte-size distribution, and the expression of genes related with adipogenesis and inflammation. WAT composition was different between groups, with SOLF samples mostly containing palmitic, myristic and lauric acids (>48% w/w) and UOLF WAT containing more than 80% (w/w) of oleic acid. In conclusion, SOLF appears to be more detrimental than UOLF to the autoparacrine leptin actions, which may have an impact on WAT inflammation. The effect of SOLF and UOLF on WAT composition may affect WAT biophysical properties, which are able to condition LepR signaling.

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A one pot alkenylation followed by a stereoselective Alder-ene cycloisomerization of cyclopropenes give (aza)spiro[2.4]heptanes and spiro[2.5]octanes in high yields. Total trans diastereoselectivity is achieved for spiro[2.4]heptanes if the cyclopropene is monosubstituted in C3. When an α,ß-unsaturatedcarbonyl-containing bromide is used, an alternative cyclization takes place giving cyclopenta[c]cyclopropa[b]pyrans.

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The use of flow methodology allows the use of alkynylphenyl vinyl ethers (benzo-fused 1,7 enynes) as substrates for the intramolecular Pauson-Khand reaction (PKr). Forced temperature and pressure conditions during a short reaction time minimize the substrate decomposition allowing the formation of the PK adduct. Substrates substituted at the internal position of the double bond and with internal triple bonds give better yields. The resulting products are cyclopentabenzofuranones present in diverse natural products and drugs that can be further functionalised.

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Ene-cyclopropenes give functionalized indanes and tetralines in the presence of ruthenium dimeric catalysts. This reaction involves the cyclopropene opening by the metal catalysts with a different regioselectivity respective to gold chlorides and produces totally different products than when using semisandwich ruthenium complexes. Here, the process leads to a bridged 7-oxanorbornene-type intermediate that is converted into a functionalized aromatic ring through deoxygenative aromatization. Alternative reaction pathways occur with substrates with no possible aromatization.

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Cyclopropanated iminosugars have a locked conformation that may enhance the inhibitory activity and selectivity against different glycosidases. We show the synthesis of new cyclopropane-containing piperidines bearing five stereogenic centers from natural amino acids l-serine and l-alanine. Those prepared from the latter amino acid may mimic l-fucose, a natural-occurring monosaccharide involved in many molecular recognition events. Final compounds prepared from l-serine bear S configurations on the C5 position. The synthesis involved a stereoselective cyclopropanation reaction of an α,ß-unsaturated piperidone, which was prepared through a ring-closing metathesis. The final compounds were tested as possible inhibitors of different glycosidases. The results, although, in general, with low inhibition activity, showed selectivity, depending on the compound and enzyme, and in some cases, an unexpected activity enhancement was observed.

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The synthesis of amides from thiols through a cobalt-catalyzed aminocarbonylation is shown. After optimizing all the reaction parameters, the methodology makes possible the obtention of amides with variable yields, while competing reactions such as the formation of disulfides and ureas can be limited. The process works well with aromatic thiols with electron donating groups (EDG) whereas other thiols give reaction with lower yields. The previous process has been transferred and optimized into flow equipment, thus allowing using less CO in a safer way, and permitting the scaling up of the synthesis. Two drugs, moclobemide and itopride were prepared with this methodology, albeit only in the second case with good results. A mechanistic pathway is proposed.

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Synthesis of four iminosugars fused to a cyclopropane ring is described using l-serine as the chiral pool. The key steps are large-scale preparation of an α,ß-unsaturated piperidinone followed by completely stereoselective sulfur ylide cyclopropanation. Stereochemistry of compounds has been studied by nuclear Overhauser effect spectroscopy (NOESY) experiments and 1H homonuclear decoupling to measure constant couplings. The activity of these compounds against different glycosidases has been evaluated. Although inhibition activity was low (compound 8a presents a (K i) of 1.18 mM against ß-galactosidase from Escherichia coli), interestingly, we found that compounds 8a and 8b increase the activity of neuraminidase from Vibrio cholerae up to 100%.

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Continuous flow reactors form part of a rapidly growing research area that has changed the way synthetic chemistry is performed not only in academia but also at the industrial level. This Review highlights the most recent advances in cycloaddition reactions performed in flow systems. Cycloadditions are atom-efficient transformations for the synthesis of carbo- and heterocycles, involved in the construction of challenging skeletons of complex molecules. The main advantages of translating these processes into flow include using intensified conditions, safer handling of hazardous reagents and gases, easy tuning of reaction conditions, and straightforward scaling up. These benefits are especially important in cycloadditions such as the copper(I)-catalyzed azide alkyne cycloaddition (CuAAC), Diels-Alder reaction, ozonolysis and [2+2] photocycloadditions. Some of these transformations are key reactions in the industrial synthesis of pharmaceuticals.

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A new synthesis of treprostinil is described using a plug flow reactor in two of the key steps. First, a Claisen rearrangement reaction is described in scaled flow at multigram amounts. Yields and selectivity of this step are sharply improved compared to those from previous syntheses. Second, the key Pauson-Khand reaction in flow is described under catalytic conditions with 5 mol% of cobalt carbonyl and only 3 equiv. of CO. Scaling up of this reaction safely ensures a good yield of an advanced intermediate which is transformed into treprostinil in three steps. Other improvements are the introduction of the carboxymethyl chain into the phenol from the beginning to reduce the protection-deprotection steps. The synthesis is completed in 14% global yield after 12 linear steps from (S)-epichlorhydrin.

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The reaction of ene-cyclopropenes with Cp*RuCl(cod) leads to alkenyl bicyclo[3.1.0]hexanes, bicyclo[4.1.0]heptanes, and bicyclo[5.1.0]octanes. This reaction involves a reverse regioselectivity in the cyclopropene opening than with gold chlorides. With gem-disubstituted cyclopropenes, a novel cycloisomerization based on ring-opening nucleophilic attack and rearrangement is observed. Alternatively, some gem-disubstituted cyclopropenes give dimerizations of the intermediate carbene.

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Long-chain multiantenna N-glycans are extremely complex molecules. Their inherent flexibility and the presence of repetitions of monosaccharide units in similar chemical environments hamper their full characterization by X-ray diffraction or standard NMR methods. Herein, the successful conformational and interaction analysis of a sialylated tetradecasaccharide N-glycan presenting two LacNAc repetitions at each arm is presented. This glycan has been identified as the receptor of the hemagglutinin protein of pathogenic influenza viruses. To accomplish this study, a N-glycan conjugated with a lanthanide binding tag has been synthesized, enabling analysis of the system by paramagnetic NMR. Under paramagnetic conditions, the NMR signals of each sugar unit in the glycan have been determined. Furthermore, a detailed binding epitope of the tetradecasaccharide N-glycan in the presence of HK/68 hemagglutinin is described.

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