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    Blended Phenotypes of Sexual Development Disorder and Coenzyme Q10 Deficiency, Together with a Sibling with Homozygous Variants in the <i>AHI1</i> Gene

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    Introduction: In consanguineous marriages, different homozygous variants in a single gene may occur in the same family. This may lead to blended phenotypes. This study presents a family in which different rare mechanisms come together as a result of consanguineous marriage. Primary coenzyme Q10 deficiency is a very rare disease that occurs due to homozygous or compound heterozygous variants in the COQ4 gene. Case Presentation: A 2-year-old proband with a blended phenotype with sex development disorder and coenzyme Q (CoQ) 10 deficiency has psychomotor retardation, dysmorphic findings, hypotonia, micropenis, and bilateral cryptorchidism. The patient's cytogenetic analysis results were compatible with SRY-positive 46,XX sex reversal disease. In the subsequent whole-exome analysis, a c.437T>G (Phe146Cys) missense homozygous probable pathogenic variant was detected in the 5th exon of the COQ4 gene (NM_016035) that explains other clinical findings. The brother of the index was previously deceased due to hydrocephalus and had a nonsense homozygous variant c.1051C>T p.(Arg351*) in the 7th exon of the AHI1 gene (NM_001134830). Discussion: Alterations in exons 5-7 of the COQ4 gene manifest early in life, resulting in neonatal fatality and a more pronounced clinical trajectory. Conversely, mutations occurring in exons 1-4 emerge later and exhibit a less severe clinical progression. Interestingly, the c.437T>G variant within exon 5 of the COQ4 gene induces comparatively milder clinical symptoms, deviating from the documented cases in the literature. To our knowledge, there is no other reported case in the literature with a blended phenotype of a sexual development anomaly and primary CoQ10 deficiency

    Diyabetik Nöropatili Hastalarda Ağrı Yönetiminde Refleksoloji Uygulaması

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    Diabetes mellitus; sinirleri, pleksusu ve/veya kökleri etkileyen çeşitli akut ve kronik nöropatilere neden olabilen kronik bir hastalıktır. Diyabetik nöropatiler yaşam kalitesinde önemli bir azalmaya yol açan DM’nin en yaygın komplikasyonudur ve diyabet hastalarının yaklaşık yarısını etkilemektedir. Diyabetik nöropatide en sık görülen semptomlardan biri ağrıdır. Nöropatik ağrıda parestezi, disestezi, hiperaljezi, allodini ve hiperpati gibi semptomlar görülür. Bu semptomlar, hastaların yaşam kalitelerini de önemli ölçüde etkilemekte, psikolojik durumlarını tehlikeye atmaktadır. Bu nedenle diyabetik nöropatili hastalarda ağrı semptomunu azaltmaya yönelik farmakolojik girişimlerin yanı sıra nonfarmakalojik girişimlerden yararlanılmaktadır. Nonfarmakolojik yöntemlerden biri olan refleksolojinin en yaygın ve etkin uygulama yöntemlerden biri olan ayak refleksolojisi, ayak tabanındaki refleks noktalarına bası yapılması sonucunda vücuttaki organ ve sistemlerin uyarılmasına dayanan yöntemlerinden biri olarak bilinmektedir. Refleksolojinin endorfin teorisine göre ayakta bulunan refleks noktalarına yapılan baskı vücuttaki endorfin salınımını uyarır. Salınan endorfin beyne giden ağrı sinyallerinin sinirsel iletimini engellemekte, kaygı ve ağrı düzeylerini azaltmakta ve bu sayede vücudun kendi kendini iyileştirmesini sağlamaktadır. Diyabetik nöropatili hastalarda ağrı tedavisinde refleksolojinin etkileri ile ilgili çalışma sayısı oldukça sınırlıdır. Bu açıdan, refleksolojinin diyabetik nöropatili hastalarda gelişen ağrıya etkisini tespit etmek için daha fazla çalışmaya ihtiyaç duyulmaktadır. Refleksoloji hemşirelerin bağımsız fonksiyonlarından biri ve hemşirelik bakımının bir parçasıdır. Bu derlemede diyabetik nörpatili hastalarda ağrı yönetimnde refleksoloji kullanımının yararları ve hemşirelikte kullanım alanlarından bahsedilecektir.&nbsp; &nbsp;</p

    Candida albicans in the oral cavities of pets: biofilm formation, putative virulence, antifungal resistance profiles and classification of the isolates

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    The study aimed to investigate Candida albicans presence, antifungal resistance, biofilm formation, putative virulence genes, and molecular characterization in oral samples of dogs and cats. A total of 239 oral samples were collected from cats and dogs of various breeds and ages at Erciyes University, Faculty of Veterinary Medicine Clinics, between May 2017 and April 2018. Among 216 isolates obtained, 15 (6.95%) were identified as C. albicans, while 8 (3.7%) were non-albicans Candida species. Antifungal susceptibility testing revealed sensitivities to caspofungin, fluconazole, and flucytosine in varying proportions. Molecular analysis indicated the presence of fluconazole and caspofungin resistance genes in all C. albicans isolates. Additionally, virulence genes ALS1, HWP1, and HSP90 showed variable presence. Biofilm formation varied among isolates, with 46.7% strong, 33.3% moderate, and 20% weak producers. PCA analysis categorized isolates into two main clusters, with some dog isolates grouped separately. The findings underscore the significance of oral care and protective measures in pets due to C. albicans prevalence, biofilm formation, virulence factors, and antifungal resistance in their oral cavity, thereby aiding clinical diagnosis and treatment in veterinary medicine

    Evaluation of the appropriateness of vancomycin therapeutic drug monitoring in the intensive care unit with a clinical pharmacy approach, a cross-sectional study

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    Objectives: Vancomycin, a glycopeptide antibiotic has antibacterial activity against Gram-positive bacteria and is frequently used in the intensive care unit (ICU). Inappropriate therapeutic drug monitoring (TDM) of vancomycin is a common problem encountered in hospital daily practice. The aim of this study was to evaluate the appropriateness of vancomycin trough-guided TDM in patients treated in the ICU using a clinical pharmacy approach. Methods: The study was conducted retrospectively in patients over 18 years old who had at least one vancomycin trough level and who had received intravenous (IV) vancomycin for ≥3 days between 1 November 2020 and 1 April 2022. The study included 137 patients. Patient demographics and relevant vancomycin TDM data were collected from medical records. The appropriateness of TDM was evaluated according to the criteria established based on the monitoring recommendations specified in consensus guidelines for therapeutic drug monitoring of vancomycin published by the American Society of Health-System Pharmacists (ASHP) in 2009 and 2020. Results: Of a total of 238 vancomycin trough levels measured in patients, 32.4% were collected at an inappropriate time. When patients were evaluated in terms of TDM appropriateness according to vancomycin level ranges (20 μg/mL), we found the appropriate TDM was significantly higher in the therapeutic range (10-20 μg/mL) (p <0.001). Of the total 238 vancomycin trough concentrations taken from patients, 77 (32.4%) were measured at an inappropriate time. This caused dose withholding, wrong adjustments and therapy failure. The total TDM appropriateness of vancomycin was significantly higher in the therapeutic range defined as 10-20 μg/mL when evaluated based on 'TDM appropriateness criteria' (p <0.001). Conclusion: Our study shows that appropriate vancomycin TDM increases the likelihood of achieving target trough concentrations. Involvement of clinical pharmacists in TDM management may prevent the development of adverse reactions by ensuring appropriate sampling time and appropriate interpretation of vancomycin levels

    Empagliflozin demonstrates cytotoxicity and synergy with tamoxifen in ER-positive breast cancer cells: anti-proliferative and anti-survival effects.

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    Accumulating evidence suggests that sodium-glucose cotransporter 2 (SGLT2) inhibitors may be effective at eliminating tumor cells. While empagliflozin exhibits nearly the highest selectivity for SGLT2 over SGLT1, its specific impact alone and in combination with tamoxifen remains largely unexplored in estrogen receptor alpha-positive (ER alpha +) breast cancer. This study investigated the anticancer effects of empagliflozin and its potential synergy with tamoxifen in MCF-7 breast cancer cells. The individual and combined cytotoxic effects of empagliflozin and tamoxifen were assessed using the xCELLigence system. The activities of AMP-activated protein kinase alpha (AMPK alpha), p38 mitogen-activated protein kinase (p38 MAPK alpha), p70-S6 kinase 1 (p70S6K1), and protein kinase B (Akt) were assessed using Western blotting. The gene expression levels of peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1 alpha) and Forkhead box O3a (FOXO3a) were assessed via qPCR. Our results revealed time- and concentration-dependent cytotoxic effects of empagliflozin and tamoxifen whether administered separately or in combination. While tamoxifen exhibits potency with an IC50 value of 17 mu M, approximately ten times greater than that of empagliflozin (IC50 = 177 mu M), synergistic effects are observed when the concentrations of the two agents approach their respective IC50 values. Additionally, empagliflozin significantly increases AMPK alpha activity while concurrently inhibiting Akt, p70S6K1, and p38 MAPK alpha, and these effects are significantly enhanced when empagliflozin is combined with tamoxifen. Moreover, empagliflozin modulates the gene expression, downregulating PGC-1 alpha while upregulating FOXO3a. Empagliflozin exerts anti-proliferative and anti-survival effects by inhibiting mTOR, Akt, and PGC-1 alpha, and it exhibits synergy with tamoxifen in MCF-7 breast cancer cells.Graphical AbstractProposed anticancer mechanism of empagliflozin in MCF-7 breast cancer cells

    Comparative Analysis of Stress and Temperature Distribution in Wire Drawing of Steel, Copper, and Aluminum

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    The wire drawing method is widely used in the metal industry for its efficiency in mass production. It is especially preferred for manufacturing items like cables and ropes, as it allows for shaping the material into the desired geometric cross section using a die. In this study, the wire drawing processes for steel, copper, and aluminum were investigated to produce circular cross-section wires, using the finite element method for analysis. Experimental studies on steel wires were conducted to validate the model's accuracy. The study examined the resultant stresses, energy release, and temperature distributions in steel, copper, and aluminum wires post-wire drawing. It also explored the effects of varying wire drawing speeds, reduction ratios, and wire diameters through numerical simulations. The findings revealed that increasing the wire drawing speed from 0.05 to 0.3 m/s led to a temperature rise of 113% in steel wires, 109% in copper wires, and 109% in aluminum wires. Similarly, a reduction ratio increases from 10 to 30% caused a temperature rise of 227% in steel wires, 197% in copper wires, and 189% in aluminum wires. These insights are crucial for determining optimal process parameters in wire drawing industry applications, offering a numerical model that enhances production efficiency

    Separation and enrichment of Cd and Pb from food and water samples based on a graphene oxide-decorated poly 2-diethylaminoethyl methacrylate nanocomposite by dispersive micro-solid phase extraction (d-μ-SPE)

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    In this study, a graphene oxide combined with poly(2-diethylaminoethyl methacrylate) (GO@PDEAEMA) nanocomposite was synthesized for the separation and enrichment of Cd and Pb from food and water samples using the dispersive micro-solid phase extraction (d-μ-SPE) technique. The GO@PDEAEMA nanocomposite was synthesized using surface-initiated atom transfer radical polymerization (SI-ATRP) and characterized using various analytical techniques, such as FTIR, FE-SEM, TGA, BET, and XRD. The optimal experimental conditions were pH 8, 0.5 M HNO₃ as eluent, 5 mg of sorbent, and adsorption/desorption times of 0.5 and 1 min, respectively, with a recovery range of 89–101 %. The suggested method showed low limits of detection (LOD) and quantification (LOQ) of 0.11 μg L−1 and 0.37 μg L−1 for Cd and 0.28 μg L−1 and 0.93 μg L−1 for Pb, respectively. The optimal procedure was successfully applied to real water and food samples. The study demonstrates the possibility of using GO@PDEAEMA nanocomposite as an effective sorbent for toxic metal extraction

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