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Finansal piyasalarda oluşabilecek fiyat hareketlerinin yönü hakkında bilgi sahibi olmak yatırımcılar, portföy yöneticileri ve riskten korunmak isteyenler için oldukça önemlidir. Finansal piyasalar hakkında tahminlerde bulunabilmek için çeşitli öncü göstergelerden faydalanılmaktadır. Bu çalışmada küresel göstergelerden olan Baltık Kuru Yük Endeksi, petrol fiyatları, altın fiyatları, Dolar Endeksi, MSCI Dünya Endeksi arasındaki volatilite yayılımı ilişkisi 02.01.2015-23.12.2021 dönemi verileri kullanılarak Antonakakis ve Gabauer (2017) tarafından geliştirilen TVP-VAR yöntemiyle araştırılmıştır. Araştırma sonucunda Baltık Kuru Yük Endeksi, Brent petrol fiyatı ve MSCI Dünya Endeksinin volatiliteyi yayan değişkenler olduğu, altın ons fiyatı ile Dolar Endeksinin volatiliteyi alan değişkenler olduğu görülmüştür. Volatiliteyi en çok yayan değişken Brent petrol fiyatı iken volatiliteyi en çok alan değişken de Dolar endeksi olmuştur. Brent petrol fiyatlarında meydana gelebilecek fiyat hareketleri takip edilerek incelenen finansal göstergelerin fiyat değişimleri hakkında bilgi sahibi olunabilecektir. Petrol fiyatlarında meydana gelen değişmelerin dünya ticaret hacmini ve sermaye hareketlerini etkilediği söylenebilmektedir. Ayrıca Covid-19 pandemisi gibi yaşanan olayların volatilitenin yönünü değiştirebileceği gözlemlenmiştir.

Objective:This study aimed to investigate the relationship between sleep quality, stress levels, and oral health-related quality of life of university students with self-reported sleep/awake bruxism in Turkey.Materials and Methods:Four anonymous questionnaires [Self-reported bruxism, perceived stress scale (PSS), Pittsburgh sleep quality index (PSQI), and oral health impact profile-14 [(OHIP-14)] were administered to 310 university student volunteers that were randomly selected from the various provinces of Turkey. The participants were required to respond independently to the questionnaires at home and were encouraged to contact the authors for further assistance if needed.Results:Among the study participants, 56.8% were from the school of dentistry and 43.2% from other departments. Of all the participants, 29% had self-reported awake bruxism and 42.3% had self-reported sleep bruxism. A positive correlation was found between the PSS and OHIP-14 results (23.5%) and between the PSQI and PSS (24.6%) results in the students with self-reported awake bruxism (p=0.235, p=0.246; p

Abstract Background Triple negative breast cancer (TNBC) is an aggressive breast cancer for which there is currently no targeted therapy. Tumor-infiltrating B-cells (TIB) have been observed in tumor tissues of TNBC patients, but their functional role is unclear. IgG4 is one of four antibody subclasses of IgG expressed and secreted by B cells. Unlike other IgG isotypes, IgG4 has an immunosuppressive function and is induced by Th2-type cytokines. In cancers such as melanoma, IgG4 has been linked with advanced disease and poor patient survival. Therefore, we sought to determine if IgG4 + B cells are present and determine the mechanisms driving isotype switching in TNBC. Methods We performed co-culture assays to examine expression of Th2 cytokines by TNBC cells with and without the presence of B cells. We also performed in vitro class switching experiments with peripheral B cells with and without co-culture with TNBC cells in the presence or absence of an IL-10 blocking antibody. We examined expression of CD20+ TIB, IgG4 and Th2 cytokines by immunohistochemistry in 152 TNBC samples. Statistical analysis was done using Log-Rank and Cox-proportional hazards tests. Results Our findings indicate that B cells interact with TNBC to drive chronic inflammatory responses through increased expression of inflammatory cytokines including the TH2 cytokines IL-4 and IL-10. In vitro class switching studies show that interactions between TNBC cell lines and B cells drive isotype switching to the IgG4 isotype in an IL-10 dependent manner. In patient tissues, expression of IgG4 correlates with CD20 and tumor expression of IL-10. Both IgG4 and tumor IL-10 are associated to shorter recurrence free survival (RFS) and overall survival (OS) in TNBC. In a multi-variant analysis, IL-10 was associated with poor outcomes indicating that tumor IL-10 may drive immune escape. Conclusions These findings indicate that interactions between TIB and TNBC results in activation of chronic inflammatory signals such as IL-10 and IL-4 that drive class switching to an IgG4 + subtype which may suppress antibody driven immune responses. The presence of IgG4 + B cells may serve as a biomarker for poor prognosis.

BackgroundNew mutational detection techniques like next-generation sequencing have resulted in an increased number of cases with uncommon mutation and compound mutations [3%–14% of all epidermal growth factor receptor (EGFR) mutations]. In rare exon 18 mutations (3%–6%), G719X and E709X represent the majority, but CMut associating these exon 18 points mutations are even rarer, making the understanding of the impact of epidermal growth factor receptor tyrosine kinase inhibitors still limited. Three generations of EGFR tyrosine kinase inhibitors (TKIs) are available to target EGFR mutations, but according to the types of mutations, the sensitivity to TKI is different. Afatinib, osimertinib, and neratinib have showed some effectiveness in single exon 18, but no report has precisely described their efficiency and acquired mechanism of resistance in a CMut of exon 18–18 (G719A and E709A).Case presentationWe report a case of a 26-year-old woman with bilateral advanced adenocarcinoma of the lung harboring a compound mutation associating G719A and E709A in exon 18, who developed an EGFR amplification as resistance mechanism to osimertinib. She presented a significant clinical and morphological response under sequential TKIs treatment (afatinib, osimertinib, and then neratinib).ConclusionA non-small cell lung cancer (NSCLC) with rare compound mutation exon 18–exon 18 (G719A and E709A) and EGFR amplification can be overcome with adapted sequential second- and third-generation TKIs. This report has potential implications in guiding decisions for the treatment of these rare EGFR mutations.

INTRODUCTION[|]This study aims to provide data from dental patients about their oral health attitudes, dental visits, oral cancer predisposing factors and general knowledge about early signs of oral cancer.[¤]METHODS[|]This study was conducted on dental examination patients, involving both genders with an age range of 12–77 years. All questions were asked through a written questionnaire.[¤]RESULTS[|]This study included 254 cases with a mean age of 31.8+-16.4 years. One hundred and fifty three (60.2%) of the study group consisted of females and 101 (39.8%) were males. Smoking and alcohol consumption were frequent among the working group and males (p=0.001). Regarding general knowledge about early cancer signs, there was no significance among genders. Considering attitudes of the last dental visits of individuals according to their occupation, the working group displayed significance (p=0.005). The total rate for information about oral cancer, causes and symptoms 20 (7.9%) individuals had positive knowledge. Only 5 (0.02%) of the participants would refer to a dentist for neck swelling.[¤]DISCUSSION AND CONCLUSION[|]General knowledge of signs and symptoms of oral cancer are low in Turkish dental patients, most declare that early diagnosis is important. The main predisposing factors of oral cancer (smoking and alcohol) are statistically more consumed by the working group but showed no gender predisposition.[¤]

Cynarin is a derivative of hydroxycinnamic acid and it has biologically active functional groups constituent of some plants and food. We elucidated the antioxidant activity of cynarin by using differentin vitrocondition bioanalytical antioxidant assays like DMPD•+, ABTS•+,, DPPH•and H2O2scavenging effects, the total antioxidant influence, reducing capabilities, Fe2+chelating and anticholinergic activities. Cynarin demonstrated 87.72% inhibition of linoleic acid lipid peroxidation at 30 µg/mL concentration. Conversely, some standard antioxidants like trolox, α-tocopherol, butylated hydroxytoluene (BHT), and butylated hydroxyanisole (BHA) exhibited inhibitions of 90.32, 75.26, 97.61, 87.30%, and opponent peroxidation of linoleic acid emulsion at the identical concentration, seriatim. Also, cynarin exhibited effective DMPD•+, ABTS•+,, DPPH•, and H2O2scavenging effects, reducing capabilities and Fe2+chelating effects. On the contrary, IC50andKiparameters of cynarin for acetylcholinesterase enzyme inhibition were determined as 243.67 nM (r2: 0.9444) and 39.34 ± 13.88 nM, respectively. This study clearly showed that cynarin had marked antioxidant, anticholinergic, reducing ability, radical-scavenging, and metal-binding activities. [ABSTRACT FROM AUTHOR]

Bu araştırmanın amacı, ortaokul öğrencilerinin ters yüz öğrenme hazırbulunuşlukları ile araştırma/sorgulamaya yönelik tutumları arasındaki ilişkiyi belirlemektir. İlişkisel tarama modelinde desenlenen bu araştırma, Van ilinde öğrenim gören 362 ortaokul öğrencisi ile gerçekleştirilmiştir. Veri toplama araçları olarak “Ortaokul Öğrencileri için Ters Yüz Öğrenme Hazırbulunuşluk Ölçeği” ve “Ortaokul Öğrencileri için Araştırma/Sorgulamaya Dönük Tutum Ölçeği” kullanılmıştır. Verilerin analizinde betimsel istatistikler, fark analizleri ve Pearson Çarpım Momentler Korelasyon Katsayısı kullanılmıştır. Araştırmanın sonucunda, ortaokul öğrencilerinin ters yüz öğrenme hazırbulunuşluklarının ve araştırma sorgulamaya yönelik tutumlarının yüksek düzeyde olduğu belirlenmiştir. Araştırmada, evinde internet bağlantısı olan ve yüksek sosyo-ekonomik gelişmişlik düzeyine sahip okullarda öğrenim gören öğrencilerin ters yüz öğrenme hazırbulunuşluklarının ve araştırma sorgulamaya yönelik tutumlarının daha yüksek olduğu saptanmıştır. Ayrıca, ortaokul öğrencilerinin araştırma sorgulamaya yönelik tutumları ile ters yüz öğrenme hazırbulunuşlukları arasında orta düzeyde, pozitif ve anlamlı bir ilişkinin olduğu sonucuna ulaşılmıştır.

Abstract Pfs48/45 is a leading antigen candidate for a transmission blocking (TB) vaccine. However, efforts to produce affordable, safe and correctly folded full-length Pfs48/45 using different protein expression systems have not produced an antigen with satisfactory TB activity. Pfs48/45 has 16 cysteines involved in disulfide bond formation, and the correct formation is critical for proper folding and induction of TB antibodies. Moreover, Pfs48⁄45 is not a glycoprotein in the native hosts, but contains potential glycosylation sites, which are aberrantly glycosylated during expression in eukaryotic systems. Here, we demonstrate for the first time that full length, Endo H in vivo enzymatic deglycosylated Pfs48/45 antigen is produced at a high level in plants and is structurally stable at elevated temperatures. Sera from mice immunized with this antigen showed strong inhibition in SMFA. Thus, Endo H in vivo enzymatic deglycosylated Pfs48/45 is a promising candidate for the development of an affordable TB vaccine, which may have the potential to save millions.

Usnic acid, as active dibenzofuran derivative, isolated and characterized from some lichen species. The aim of manuscript was to evaluate antioxidant, anticholinergic and antidiabetic potentials of usnic acid as an important natural product. Antioxidant profile of usnic acid determined by eight distinguishes bioanalytical antioxidant methods including 1,1-diphenyl-2-picrylhydrazyl (DPPH·), 2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS·+), superoxide anion radical (O2·−) and N,N-dimethyl-p-phenylenediamine (DMPD·+) scavenging activities, cupric ion (Cu2+), ferric ion (Fe3+) and Fe3+-TPTZ reducing abilities and ferrous ion (Fe3+) chelating activity. Usnic acid was found as potent DPPH· (IC50: 49.50 μg/mL), DMPD·+ (IC50: 33.00 μg/mL), O2·− (IC50: 18.68 μg/mL), and ABTS·+ (IC50: 10.41 μg/mL) scavenging effects. Also, the inhibition effects of usnic acid were tested against some metabolic enzymes including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) linked to neurodegenerative diseases. Both enzymes play important roles in cholinergic transmission by hydrolyzing the neurotransmitter acetylcholine in cholinergic synapses, central nervous system, neuromuscular junctions and autonomic ganglia. Their inhibitors were used for clinical treatment of some neurodegenerative conditions including myasthenia gravis, Alzheimer's disease, apathy, glaucoma, postural tachycardia syndrome and dementia. Furthermore, usnic acid showed the potent inhibition profiles against AChE (IC50: 1.273 nM) and BChE (IC50: 0.239 nM) enzymes. The results clearly showed that usnic acid is an important natural product with antioxidant and anticholinergic potentials. Keywords: Usnic acid, Antioxidant activity, Acetylcholinesterase, Butyrylcholinesterase, Enzyme inhibition

Abstract Background Immunotherapy represents a new therapeutic approach in non-small cell lung carcinoma (NSCLC) with the potential for prolonged benefits. Because of the systemic nature and heterogeneity of tumoral diseases, as well as the immune restoration process induced by immunotherapy, the assessment of therapeutic efficacy is challenging, and the role of FDG PET is not well established. We evaluated the potential of FDG PET to monitor NSCLC patients treated with a checkpoint inhibitor. Results This was a retrospective analysis of 28 NSCLC patients treated with nivolumab, a programmed cell death 1 (PD-1) blocker. All patients underwent a PET scan before treatment (SCAN-1) and another scan 2 months later (SCAN-2). Disease progression was assessed by immune PET Response Criteria in Solid Tumors (iPERCIST), which was adapted from PERCIST; and the immune Response Evaluation Criteria in Solid Tumors (iRECIST). iPERCIST is a dual-time-point evaluation of “unconfirmed progressive metabolic disease” (UPMD) status at SCAN-2. UPMD at SCAN-2 was re-evaluated after 4 weeks with SCAN-3 to confirm PMD. Patients with complete/partial metabolic response (CMR or PMR) or stable metabolic disease (SMD) at SCAN-2 or -3 were considered responders. Patients with UPMD confirmed at SCAN-3 were considered non-responders. The Kaplan-Meier method was used to estimate survival. At SCAN-2, we found 9/28 cases of PMR, 4/28 cases of SMD, 2/28 cases of CMR, and 13/28 cases of UPMD. Four of the 13 UPMD patients were classified as responders at SCAN-3 (PMR n = 1, SMD n = 3). The remaining nine UPMD patients were classified as non-responders due to clinical degradation, and treatment was stopped. The median follow-up was 16.7 months [3.6–32.2]. Responders continued treatment for a mean of 10.7 months [3.8–26.3]. Overall survival was longer for responders than that for non-responders (19.9 vs. 3.6 months, log rank p = 0.0003). The 1-year survival rates were 94% for responders and 11% for non-responders. A comparison with iRECIST showed reclassification in 39% (11/28) of patients with relevant additional prognostic information. Conclusions iPERCIST dual-time-point evaluation might be a powerful tool for evaluating anti-PD-1-based immunotherapy, with the ability to identify patients who can benefit most from treatment. The prognostic value of iPERCIST criteria should be confirmed in large prospective multicentric studies.

Ethanolic (EEC) and aqueous (WEC) extracts of cinnamon (Cinnamomum verum) were evaluated for their antioxidant profiles by eight distinguished bioanalytical antioxidant methods. Their inhibitory effects were tested against some enzymes including acetylcholinesterase, butyrylcholinesterase, α-glycosidase and α-amylase, which linked to different diseases. Additionally, the antioxidant properties were determined and polyphenolic compositions of the both extracts were evaluated by LC-MS/MS analysis. According to the LC-MS/MS experiments, thirteen compounds were found in WEC and EEC. Also, p-hydroxybenzoic acid (321.1 mg/kg extract), p-coumaric acid (291.4 mg/kg extract), and pyrogallol (142.4 mg/kg extract) were found to be the most abundant ingredients in the WEC. On the other hand, pyrogallol (264.3 mg/kg extract), ferulic acid (224.7 mg/kg extract) and p-coumaric acid (170.2 mg/kg extract) were found as the most plentiful chemicals in the EEC. For the estimation of the antioxidant capacities of the both extracts (WEC and EEC), DPPH· and ABTS•+ scavenging activities, as well as Fe3+-Fe2+, and Cu2+-Cu+ reducing assays were studied. The IC50 values of the WEC and EEC indicated that they were potent effective DPPH· (21. 25 and 15.71 μg/mL) and ABTS•+ (6.52 and 5.79 μg/mL) scavengers, as well as AChE (221.33 and 110.26 μg/mL), BChE (461.69 and 94.93 μg/mL), α-glycosidase (206.86 and 220.00 μg/mL) and α-amylase (189.86 and 200.86 μg/mL) inhibitors. As a conclusion, both EEC and WEC had rich phenolic contents and demonstrated effective anticholinergic, antidiabetic and antioxidant effects.

Introduction: Platin-based chemotherapy (CT) has long been the first-line standard-of-care for patients with extensive-stage small-cell lung cancer (ES–SCLC). Adding immune-checkpoint inhibitor(s) to CT (ICI+CT) in this setting is an option of interest, although its benefit is apparently modest. Methods: This meta-analysis was conducted on randomized trials comparing first-line ICI+CT versus CT alone for ES–SCLC. Outcomes included overall survival (OS), progression-free survival (PFS), objective response rate (ORR), response at 12 months and adverse events (AEs). Subgroup analyses were computed according to the immunotherapy used, performance status (PS), age, platinum salt, liver metastases and brain metastases at diagnosis. Results: The literature search identified one randomized phase II (ECOG-ACRIN-5161) and four phase III trials (CASPIAN, IMPOWER-133, KEYNOTE-604 and Reck et al. 2016) that included 2775 patients (66% males, 95% smokers, median age: 64 years, PS = 0 or 1). ICI+CT was significantly associated (hazard ratio [95% confidence interval]) with prolonged OS [0.82 (0.75–0.89); p

A plant expression platform with eukaryotic post-translational modification (PTM) machinery has many advantages compared to other protein expression systems. This promising technology is useful for the production of a variety of recombinant proteins including, therapeutic proteins, vaccine antigens, native additives, and industrial enzymes. However, plants lack some of the important PTMs, including furin processing, which limits this system for the production of certain mammalian complex proteins of therapeutic value. Furin is a ubiquitous proprotein convertase that is involved in the processing (activation) of a wide variety of precursor proteins, including blood coagulation factors, cell surface receptors, hormones and growth factors, viral envelope glycoproteins, etc. and plays a critical regulatory role in a wide variety of cellular events. In this study, we engineered the human furin gene for expression in plants and demonstrated the production of a functional active recombinant truncated human furin in N. benthamiana plant. We demonstrate that plant produced human furin is highly active both in vivo and in vitro and specifically cleaved the tested target proteins, Factor IX (FIX) and Protective Antigen (PA83). We also demonstrate that both, enzymatic deglycosylation and proteolytic processing of target proteins can be achieved in vivo by co-expression of deglycosylating and furin cleavage enzymes in a single cell to produce deglycosylated and furin processed target proteins. It is highly expected that this strategy will have many potential applications in pharmaceutical industry and can be used to produce safe and affordable therapeutic proteins, antibodies, and vaccines using a plant expression system.

In 2018, dosing regimens of the two most prescribed immune check point inhibitors (ICI), nivolumab (Opdivo®) and pembrolizumab (Keytruda®), in the treatment of lung cancer were changed from weight-based dosing to fixed dosing. The aim of this study was to compare the economic impact of this change in our university hospital group and then across Ile-de-France, the most inhabited French region. A budget impact analysis (BIA) has been performed on the French public health insurance data. The duration of treatment and the weight of the patients were calculated using data from the patients treated at our health facility and from clinical studies. The cost of treatment was calculated at the local level of our health facility and then for Ile-de-France. Our model demonstrates an additional cost of €550,115 in our hospital and €9,704,778 in Ile-de-France for a fixed dose prescription in 2018. In 2019, the BIA concluded an additional cost, according to the respective low and high assumptions, of €556,969 and €756,544 locally and € 10,201,027 to €14,486,141 for Ile-de-France for an equivalent efficacy between the two different drug dosing regimens of nivolumab and pembrolizumab. The adoption of the fixed dose regimen would lead, according to the least expensive hypothesis, to an additional cost of 26% for the ICI. These results encourage reflection on the strict adoption of this dosage modification. The option of maintaining the free choice between a prescription adapted to weight or in a fixed dose seems a relevant option and should be considered.

O artigo trata dos movimentos sociais pelo transporte coletivo no Brasil, enfatizando suas trajetórias, agendas e estratégias de luta pelo acesso ao transporte, entendido como condição imprescindível não apenas para a democratização do espaço urbano, mas também para o acesso aos direitos civis, políticos, sociais, econômicos, culturais e ambientais. A revisão de literatura revela que na trajetória analisada os movimentos pelo transporte recorreram a diferentes estratégias: de manifestações espontâneas como os quebra-quebras e interdição de vias públicas à organização em coletivos abertos e descentralizados; de reivindicações contra o aumento no preço das passagens e protestos contra as péssimas condições de manutenção dos veículos à luta pela gratuidade e estatização do sistema, revelando assim o caráter radical e anticapitalista que adquiriram as lutas desencadeadas nos últimos anos.

A plant transient expression system, with eukaryotic post-translational modification machinery, offers superior efficiency, scalability, safety, and lower cost over other expression systems. However, due to aberrant N-glycosylation, this expression system may not be a suitable expression platform for proteins not carrying N-linked glycans in the native hosts. Therefore, it is crucial to develop a strategy to produce target proteins in a non-glycosylated form while preserving their native sequence, conformation and biological activity. Previously, we developed a strategy for enzymatic deglycosylation of proteins in planta by co-expressing bacterial peptide-N-glycosidase F (PNGase F). Though PNGase F removes oligosaccharides from glycosylated proteins, in so doing it causes an amino acid change due to the deamidation of asparagine to aspartate in the N-X-S/T site. Endo-β-N-acetylglucosaminidase (EC3.2.1.96, Endo H), another deglycosylating enzyme, catalyzes cleavage between two N-Acetyl-D-glucosamine residues of the chitobiose core of N-linked glycans, leaving a single N-Acetyl-D-glucosamine residue without the concomitant deamidation of asparagine. In this study, a method for in vivo deglycosylation of recombinant proteins in plants by transient co-expression with bacterial Endo H is described for the first time. Endo H was fully active in vivo. and successfully cleaved N-linked glycans from glycoproteins were tested. In addition, unlike the glycosylated form, in vivo Endo H deglycosylated Pfs48/45 was recognized by conformational specific Pfs48/45 monoclonal antibody, in a manner similar to its PNGase F deglycosylated counterpart. Furthermore, the deglycosylated PA83 molecule produced by Endo H showed better stability than a PNGase F deglycosylated counterpart. Thus, an Endo H in vivo deglycosylation approach provides another opportunity to develop vaccine antigens, therapeutic proteins, antibodies, and industrial enzymes.

PURPOSE:Texture indices (TI) calculated from 18F-FDG PET tumor images show promise for predicting response to therapy and survival. Their calculation involves a resampling of standardized uptake values (SUV) within the tumor. This resampling can be performed differently and significantly impacts the TI values. Our aim was to investigate how the resampling approach affects the ability of TI to reflect tissue-specific pattern of metabolic activity. METHODS:18F-FDG PET were acquired for 48 naïve-treatment patients with non-small cell lung cancer and for a uniform phantom. We studied 7 TI, SUVmax and metabolic volume (MV) in the phantom, tumors and healthy tissue using the usual relative resampling (RR) method and an absolute resampling (AR) method. The differences in TI values between tissue types and cancer subtypes were investigated using Wilcoxon's tests. RESULTS:Most RR-based TI were highly correlated with MV for tumors less than 60 mL (Spearman correlation coefficient r between 0.74 and 1), while this correlation was reduced for AR-based TI (r between 0.06 and 0.27 except for RLNU where r = 0.91). Most AR-based TI were significantly different between tumor and healthy tissues (pvalues

Background. Physical activity (PA) reduces incidence of colorectal cancer (CRC). Its influence on cancer-specific (CSS) and overall survival (OS) is controversial. Methods. We performed a literature-based meta-analysis (MA) of observational studies, using keywords “colorectal cancer, physical activity, and survival” in PubMed and EMBASE. No dedicated MA was found in the Cochrane Library. References were cross-checked. Pre- and postdiagnosis PA levels were assessed by MET. Usually, “high” PA was higher than 17 MET hour/week. Hazard ratios (HRs) for OS and CSS were calculated, with their 95% confidence interval. We used more conservative adjusted HRs, since variables of adjustment were similar between studies. When higher PA was associated with improved survival, HRs for detrimental events were set to

A letter to the editor is presented in response to the article relating to denial of flu vaccination for student nurses in the previous issue.

Purpose: Diabetes remains a prevalent metabolic chronic condition. The pandemic promoted the use of telemedicine for patients with chronic conditions. Telemedicine offers innovative methods to achieve glycemic control for these patients. This study evaluates the effectiveness of telemedicine with pharmacists in reduction of glycated hemoglobin (A1C) for patients with diabetes. Methods: This study ( n  = 112) was a single-center, retrospective study that evaluated the effectiveness of patients enrolling in pharmacist-led diabetes management utilizing telemedicine during the COVID-19 pandemic. Patients with an A1C >9 mg/dL were contacted for telemedicine with the pharmacy team. The three groups included: patients agreeing to the telemedicine visit ( n  = 28), patients that declined the telemedicine visit ( n  = 42), and patients that did not answer the telephone when offered the telemedicine visit ( n  = 28). Results: Our study revealed a significant change in the primary endpoint A1C (2.6 + 2.4, p  = 0.0144) for the patients who accepted telemedicine visits when compared with the other study groups. The secondary endpoints, changes in A1C (when evaluating employment status, number of clinic visits, number of chronic conditions, gender, race) and changes in body mass index, revealed no significant changes. Conclusion: Diabetes management using telemedicine with pharmacists impacts glycemic control in patients with type 2 diabetes. This study demonstrates patients who accepted pharmacist-led telemedicine had a reduction in A1C. Further research may reveal long-term benefits on clinical outcomes after utilizing this service during the COVID-19 pandemic.

Azathioprine is used to treat the symptoms of rheumatoid arthritis and for the prevention of transplant rejection. A review of the therapeutic uses of Azathioprine reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of Azathioprine currently exists. Azathioprine is commercially available only as a 50-mg tablet. An extemporaneously compounded suspension from pure drug powder would provide a flexible, customizable option to meet unique patient needs with convenient and accurate dosing options. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded Azathioprine suspensions in the PCCA Base, SuspendIt. This base is a sugar-free, paraben free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two Azathioprine concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating high-performance liquid chromatographic assay for the determination of the chemical stability of Azathioprine in PCCA SuspendIt was developed and validated. Suspensions of Azathioprine were prepared in PCCA SuspendIt at 10-mg/mL and 50-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in amber plastic prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially, and on the following time points (days): 7, 14, 28, 49, 63, 90, 119, and 182. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The study showed that Azathioprine concentrations did not go below 96.8% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. The pH values remained constant. The viscosity of the suspensions allowed easy re-dispersal of the drug particles upon shaking. This study demonstrates that Azathioprine is physically, chemically, and microbiologically stable in PCCA SuspendIt for 182 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for Azathioprine in a liquid dosage form, with an extended beyond-use date to meet patient needs., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

Pyrimethamine is an antiparasitic compound available only in tablet form for oral administration. A review of the therapeutic uses of pyrimethamine reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of pyrimethamine currently exists. Pyrimethamine is available commercially only as 25-mg tablets. An extemporaneously compounded suspension from pure drug powder would provide a flexible, customizable option to meet unique patient needs with convenient and accurate dosing options. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded pyrimethamine suspension in PCCA Base, SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. A robust stability-indicating high-performance liquid chromatographic assay for the determination of the chemical stability of pyrimethamine in PCCA SuspendIt was developed and validated. Suspensions of pyrimethamine were prepared in PCCA SuspendIt at a 2-mg/mL concentration, selected to provide flexibility in customizing individual doses. Samples were stored in amber plastic prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially, and on the following time points (days): 7, 14, 28, and 42. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The study showed that pyrimethamine concentrations did not go below 96% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. pH values remained constant. The viscosity of the suspensions allowed easy re-dispersal of the drug particles upon shaking. This study demonstrates that pyrimethamine is physically, chemically, and microbiologically stable in PCCA SuspendIt for 42 days stored in the refrigerator and at room temperature, thus providing a viable, compounded alternative for pyrimethamine in a liquid dosage form., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

Amitriptyline hydrochloride is indicated for the relief of symptoms of depression. A review of the therapeutic uses of amitriptyline hydrochloride reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of amitriptyline currently exists. Amitriptyline hydrochloride is commercially available only as 10-mg, 25-mg, 50-mg, 75-mg, 100-mg, and 150-mg tablets. An extemporaneously compounded suspension from pure drug powder would provide a flexible, customizable option to meet unique patient needs with convenient and accurate dosing options. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded amitriptyline hydrochloride suspensions in PCCA Base, SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two amitriptyline hydrochloride concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability- indicating high-performance liquid chromatographic assay for the determination of the chemical stability of amitriptyline hydrochloride in PCCA SuspendIt was developed and validated. Suspensions of amitriptyline hydro- chloride were prepared in PCCA SuspendIt at 1-mg/mL and 5-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in amber plastic prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially, and on the following time points (days): 7, 14, 28, 49, 63, 91, 119, and 185. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The study showed that amitriptyline hydrochloride concentrations did not go below 99.8% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. The pH values remained constant. The viscosity of the suspensions allowed easy re-dispersal of the drug particles upon shaking. This study demonstrates that amitriptyline hydrochloride is physically, chemically, and microbiologically stable in PCCA SuspendIt for 185 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for amitriptyline hydrochloride in a liquid dosage form, with an extended beyond-use date to meet patient needs., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

Hydrocortisone is indicated in the treatment of primary or secondary adrenal insufficiency. The oral dosage regimen of hydrocortisone needs to be individualized in the treatment of congenital adrenal hyperplasia, especially in pediatric patients. A review of the therapeutic uses of hydrocortisone reveals the need for flexibility in dosing. This flexibility is readily achieved using an oral liquid dosage form. However, no commercial liquid dosage form of hydrocortisone currently exists. Hydrocortisone is commercially available as 5-mg, 10-mg, and 20-mg tablets. An extemporaneously compounded suspension from pure drug powder would provide a convenient option to meet unique patient needs. The purpose of this study was to determine the physicochemical and microbiological stability of extemporaneously compounded hydrocortisone suspensions in PCCA Base, SuspendIt. This base is a sugar-free, paraben-free, dye-free, and gluten-free thixotropic vehicle containing a natural sweetener obtained from the monk fruit. The study design included two hydrocortisone concentrations to provide stability documentation over a bracketed concentration range for eventual use by compounding pharmacists. A robust stability-indicating high-performance liquid chromatographic assay for the determination of the chemical stability of hydrocortisone in SuspendIt was developed and validated. Suspensions of hydrocortisone were prepared in SuspendIt at 1-mg/mL and 20-mg/mL concentrations, selected to represent a range within which the drug is commonly dosed. Samples were stored in plastic amber prescription bottles at two temperature conditions (5°C and 25°C). Samples were assayed initially and on the following days: 7, 15, 28, 45, 60, 91, 120, and 185. Physical data such as pH, viscosity, and appearance were also noted. Microbiological stability was tested. All measurements were obtained in triplicate. A stable extemporaneous product is defined as one that retains at least 90% of the initial drug concentration throughout the sampling period and is protected against microbial growth. The study showed that hydrocortisone concentrations did not go below 94% of the label claim (initial drug concentration) at both temperatures studied. No microbial growth was observed. Viscosity and pH values did not change significantly. This study demonstrates that hydrocortisone is physically, chemically, and microbiologically stable in SuspendIt for 185 days in the refrigerator and at room temperature, thus providing a viable, compounded alternative for hydrocortisone in a liquid dosage form, with an extended beyond-use date to meet patient needs., (Copyright© by International Journal of Pharmaceutical Compounding, Inc.)

To describe the change in the epidemiology of health care-associated infections (HAI), resistance and predictors of fatality we conducted a nationwide study in 24 hospitals between 2015 and 2018. The 30-day fatality rate was 22% in 2015 and increased to 25% in 2018. In BSI, a significant increasing trend was observed for Candida and Enterococcus. The highest rate of 30-day fatality was detected among the patients with pneumonia (32%). In pneumonia, Pseudomonas infections increased in 2018. Colistin resistance increased and significantly associated with 30-day fatality in Pseudomonas infections. Among S. aureus methicillin, resistance increased from 31 to 41%., (© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.)

Nephrotoxicity has been associated with nucleos(t)ide analogues other than telbivudine (LdT). This study investigated the potential effects of LdT and lamivudine (LAM) on renal function in an experimental rat model of gentamicin-induced acute nephrotoxicity. A total of 28 healthy Wistar albino rats were randomly divided into four experimental groups: negative control; positive control (PC); LdT; and LAM. Nephrotoxicity was induced by gentamicin in the LdT, LAM and PC groups. LdT and LAM were administered to two groups for 6 weeks starting on the ninth day. Blood samples were collected weekly and cystatin C levels were measured by ELISA. Animals were sacrificed on the 50th day and the kidneys were removed for histological examination. Serum cystatin C levels differed significantly between the LdT and LAM groups (P <0.007) and between the LdT and PC groups (P <0.001). Renal function was significantly improved in the LdT group at the start of antiviral treatment on Day 8 and at the end of treatment on Day 50 (P = 0.001 and 0.007). Glomerular injury, acute tubular necrosis and total injury score were significantly reduced in the LdT group relative to the PC and LAM groups upon histopathological examination. LdT was associated with significant improvements in renal function as measured by biochemical and histopathological methods. The acute kidney injury model data should be supported by clinical studies to suggest that LdT treatment may have advantages for patients with underlying chronic kidney disease receiving chronic hepatitis B treatment., (Copyright © 2017 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.)

Background: The aim of this study was to assess health-related quality of life (HRQOL) among chronic hepatitis B (CHB) patients in Turkey and to study related factors., Methods: This multicenter study was carried out between January 01 and April 15, 2015 in Turkey in 57 centers. Adults were enrolled and studied in three groups. Group 1: Inactive HBsAg carriers, Group 2: CHB patients receiving antiviral therapy, Group 3: CHB patients who were neither receiving antiviral therapy nor were inactive HBsAg carriers. Study data was collected by face-to-face interviews using a standardized questionnaire, Short Form-36 (SF-36) and Hepatitis B Quality of Life (HBQOL). Values equivalent to p < 0.05 in analyses were accepted as statistically significant., Results: Four thousand two hundred fifty-seven patients with CHB were included in the study. Two thousand five hundred fifty-nine (60.1 %) of the patients were males. Groups 1, 2 and 3, consisted of 1529 (35.9 %), 1721 (40.4 %) and 1007 (23.7 %) patients, respectively. The highest value of HRQOL was found in inactive HBsAg carriers. We found that total HBQOL score increased when antiviral treatment was used. However, HRQOL of CHB patients varied according to their socio-demographic properties. Regarding total HBQOL score, a higher significant level of HRQOL was determined in inactive HBV patients when matched controls with the associated factors were provided., Conclusions: The HRQOL score of CHB patients was higher than expected and it can be worsen when the disease becomes active. Use of an antiviral therapy can contribute to increasing HRQOL of patients.

Amputee patients commonly experience skin problems that may result in social, mental, and economic difficulties. The purpose of this study was to evaluate the incidence of dermatological disorders and identify potential causes and symptomatic patterns among a population of lower limb amputees. Seventy lower limb amputees were enrolled. Complete examinations were performed by a dermatologist, who diagnosed and documented any skin disorders observed and recorded demographic characteristics of each patient. Mycological and bacteriological swabs were collected from the skin at the amputation site for culture analysis. In patients with suspected disease, patch tests were performed. Of the 70 patients, 58 (82.9%) were male and 12 (17.1%) female. Vascular insufficiency due to diabetes (n = 38, 54.3%) and trauma (n = 16, 22.9%) were the most common reasons for amputation. Skin problems were observed in 49 (70%) cases, and positive allergen reactions occurred in 16 (45.7%) of the 35 contact dermatitis cases. Fungal infection occurred in two patients and bacterial infection in seven. Seventy percent of the lower limb amputee patients in this cohort exhibited skin problems. This high percentage indicates that skin problems may reduce patients' quality of life. A multidisciplinary approach to the treatment of patients who have undergone amputation and early recognition and treatment of symptoms are therefore of critical importance., (© 2015 The International Society of Dermatology.)