A recent alternative to QTH, LED curing

A recent alternative to QTH, LED curing http://www.selleckchem.com/products/baricitinib-ly3009104.html units are increasingly used in dental practice. The LED has the advantages of extended of lifetimes of over 10000 h, little degradation of light output over time, and resistance to shock, overheating, and vibration.2 The spectral output of LEDs consists of the absorption peak of CQ (400�C500 nm, peak at 470 nm), the most used photoinitiator in resin composites. Comparative studies demonstrated that the type of LCU is an important factor for both curing efficiency and generated heat.8,9 However, few studies have investigated the cytotoxicity of composites with different curing methods. The determination of the possibly toxic effect of composites is a matter of interest. In view of the great variety of LCUs and filling materials currently in use, the question is which combinations cause the least toxic effects.

The present study aimed to explore, in an in vitro model, the possible cytotoxicity of various composite�CLCU combinations. MATERIALS AND METHODS Sample preparation The A3 shades of composites Filtek P60, Filtek A110, Filtek Supreme, Filtek Z250 (3M ESPE, St. Paul, MN, USA) and SDI Rok (SDI Ltd., Victoria, Australia) were evaluated in this study. The composition of each material is detailed in Table 1. For each material, disc-shaped samples (2 mm diameter and 2 mm in thickness) were prepared using Teflon molds. These molds were placed on flat glass plates on top of Mylar strips (Moyco Union Broach, York, USA) and then filled in bulk with composites. The composites were then covered with an acetate strip and gently pressed with another flat glass plate.

Next, excess material was removed with a scalpel (Otto R��ttgers GmBH, Solingen, Germany). The top glass plate was removed to polymerize the samples. The samples were polymerized and randomly divided into two groups (n=6/group) according to the LCU: 1) QTH/40secs (Optilux 501, Kerr, Orange, CA) and 2) LED/20secs (Elipar Freelight II, 3M/ESPE, Seefeld, Germany). The LCUs were all used in standard mode (continuous, constant light intensity). Before photoactivation, the irradiance of both curing units was confirmed with QTH and LED radiometers (Kerr/Demetron, Orange, CA, USA). The output spectrum for the LED was concentrated within the 425�C500 nm wavelength range, while that of the Optilux 501 is considerably wider (375�C520 nm).

However, the spectral flux of the LED was much higher at 425�C475 nm, the effective range of CQ the photo-initiator for both resins (Figure 1). Figure Batimastat 1. Cell viability of the samples polymerized by LED and QTH light curing units. Table 1. Materials, manufacturers, and approximate resin composition (According to manufacturers�� information). Cell proliferation The cells used for the experiment were L929 mouse fibroblasts. The cells were grown as monolayer cultures in 25T-flasks (Corning, NY, USA) in Dulbecco��s Modified Eagle��s Medium/F12 (DMEM/F12) (Sigma Chemical Co. St.

From the sponsor’s perspective it is monitor’s responsibility

From the sponsor’s perspective it is monitor’s responsibility www.selleckchem.com/products/Tipifarnib(R115777).html to verify that source documents and other trial records are accurate, complete, and appropriately maintained. Once AV recording becomes a regulatory requirement in India, the monitor would be required to review the IC process and bring any deficiencies to the notice of investigator. The monitor will have to take all reasonable precautions within the applicable regulatory framework to maintain confidentiality of subjects?? identity and ensure that these recordings are maintained under secured access. Extensive training will have to be imparted to the monitor to fulfill this responsibility. Language barrier In case of audits and inspections, it will become challenging for auditor/inspector to confirm if the process was adequately performed since he or she may not familiar with the language used and may need a translator.

Cost implication The cost implication of recording consent process for each and every informed consent discussion cannot be undermined. The activity has a potential to shoot the clinical trial budget significantly. Consider in a study with large sample size and high screen failure rate, each and every informed consent discussion will have to be recorded, irrespective of whether the participant agrees or refuses to consent at the end of the discussion. In addition, the records of all participants who have consented but screen failed due to any inclusion and exclusion criteria will have to be archived, which adds to the cost.

Special populations AV recording of the consent process in studies enrolling patients treated in emergency conditions and critical cases will be a problem. In addition, for the illiterate Brefeldin_A patients, the impartial witness and for participants not able to consent for themselves selleck inhibitor a LAR will have to be included in the recording. The assent from the minor will also have to be captured in the recording. Risk of tampering the records The ICFs are maintained with original signatures and though tampering the signed document is possible, it is quite difficult and may be relatively easier to detect. However with advances in technology, tampering of the AV recording may become easier and difficult to detect. Hence, ensuring controlled access and robust IT policies (including an audit trail) will be required in order to be in place to avoid any misuse of the records. How long would this information be stored for and what happens at the end of a trial would need to be defined and discussed with the regulators. CONCLUSION AV recording of the consent process will definitely help to record the actual consent process, but ascertaining that the participant has voluntarily consented still remains debatable.

The rationale for testing DHA was strong It is enriched in neuro

The rationale for testing DHA was strong. It is enriched in neuronal membranes but depleted in AD. Multiple epidemiological studies report diets rich in fish or DHA reduce AD risk, most clearly in non-apolipoprotein E4 (ApoE4) carriers [1]. Preclinical studies with DHA have not yet modeled ApoE isoform pharmacogenomics, sellckchem but mice transgenic for familial dominant AD mutations that elevate ??-amyloid (A??) production are vulnerable to dietary DHA depletion. DHA and its metabolites pleiotropically impact A?? production, insulin/neurotrophic signaling, tau kinase activation and synaptic plasticity [1]. Although DHA had no impact on cognitive or functional decline based on intent to treat AD, in non-ApoE4 carriers, DHA supplementation appeared to reduce declines in MMSE and Alzheimer Disease Assessment Scale-Cognitive (ADAS-Cog).

This commentary discusses the trial’s results and important questions raised, including the need for optimization of dose and antioxidant combinations and whether there should be further investigation of the impact of DHA on slowing cognitive decline in non-ApoE4 carriers. Perhaps a larger issue is whether agents directed at amyloid or tau pathology or associated with reduced AD risk should be translated with an intent-to-treat earlier disease stages rather than mild to moderate AD. The randomized trial of DHA for AD provides evidence that DHA supplementation provides no general benefit to AD patients, including no overall impact on Clinical Dementia Rating (CDR) scale, ADAS- Cog, MMSE, Neuropsychiatric Inventory (NPI; P = 0.

11) and Activities of Daily Living (ADL) [2]. The authors argue that DHA may still have potential for prevention. Thus, a fundamental question arising out of this study is the stage at which we should treat. First, three smaller studies showed an apparent benefit from fish oil treatment in mild cognitive impairment but not in mild to moderate AD subjects [3-5]. With age-associated memory impairment, one small trial [6] and the larger 485-subject Carfilzomib MIDAS (Memory Improvement with DHA Study) trial [7] found significant cognitive benefits with DHA. While there have been two fish oil trials in unimpaired elderly in which no cognitive selleck chemicals Pazopanib benefits were observed [8,9], subjects in both were cognitively normal at baseline, and the latter failed to show significant cognitive decline in the placebo group. Th is study argues that fish oil is not a cognitive enhancer, but does not examine disease modification in subjects with pathology-driven memory deficits.

3 Genetic effects Apolipoprotein E (APOE) ??4 is the most import

3. Genetic effects Apolipoprotein E (APOE) ??4 is the most important known genetic risk factor for typical late-onset AD. The lifetime risk HTC of developing AD is increased and the age of onset of the disease is decreased with increasing number of APOE ??4 alleles [64]. Studies have shown that APOE ??4 carriers and non-carriers have dissimilar functional connectivity networks in younger adults [65] as well as older adults [51,66]. In a recent study, Sheline and colleagues [67] showed that there is altered connectivity in APOE ??4 carriers before the onset of amyloid plaque formation, suggesting that the genetic effect of APOE is seen even before any pathological changes. These studies suggest that it is important to take into account the functional architecture differences due to genetics. 4.

Amyloid deposition and functional connectivity in Alzheimer’s disease Amyloid deposition is widely believed to be an early process in AD and by itself does not directly cause clinical symptoms [68]. Pittsburgh compound B (PIB) PET scans have commonly been used as a surrogate for amyloid deposition [69] in recent fMRI AD studies. Recent literature has consistently shown that there is a disruption of functional connectivity (especially, DMN) in subjects with amyloid deposition but no cognitive impairment [43,44,49,70-72]. However, whether these early changes to the functional architecture are a compensatory mechanism to amyloid toxicity or a cause of amyloid deposition needs to be further investigated [73]. 5.

Measuring efficacy of therapeutics At present, AD biomarkers have not yet been validated as surrogate endpoints for regulatory purposes and therefore Carfilzomib cannot be used as the primary indicators of efficacy. However, there is a search for biomarkers that are non-invasive (to use for serial measurements) as well as sensitive (to perform clinical trials with smaller sample sizes). fMRI has always been viewed as a potential candidate since it can capture subtle pharmacodynamic effects on brain connectivity. TF-fMRI is of particular interest since its effect size is 2.4 times better than that of encoding-associated fMRI techniques in distinguishing risk groups and much easier to set up on clinical scanners because no additional specialized hardware or software is needed [66]. A recent study showed that TF-fMRI can detect the effect of symptomatic treatment for moderate AD over 6 months [74].

6. Differential diagnosis of dementias Given that pathology does not always map onto the clinical expression of the disease and has considerable clinical heterogeneity, biomarkers (such as TF-fMRI) that can provide information about the various functional networks may aid in the differential diagnosis of dementia types. Functional deactivation contain [75] and rs-fMRI differences [76] have been shown to be different between subjects with dementia with Lewy bodies and AD.

The new research diagnostic criteria for AD and MCI allow for A??

The new research diagnostic criteria for AD and MCI allow for A?? imaging in the workup of individuals selleck bio with cognitive impairment [5,6]. Non-invasive A?? imaging to confirm the presence of AD neuropathology could aid in early differential diagnosis, identify at-risk individuals, help predict or monitor disease progression, and potentially evaluate the response to disease-specific therapy. 11C-Pittsburgh Compound B (PiB) has been the most widely used agent in dementia research to assess A?? burden in vivo [7]. The major disadvantage of PiB is that it is radiolabeled with carbon-11, which has a short decay half-life (20 minutes) that limits its use to centers with an onsite cyclotron and 11C-radiochemistry expertise.

To overcome these limitations, a number of novel fluorine-18 A?? imaging tracers such as 18F-florbetaben (BAY 94-9172) [8-10], 18F-florbetapir (AV45) [11,12] and 18F-flutemetamol (GE067) [13,14] have been developed. The 110-minute radioactive decay half-life of fluorine-18 allows centralized synthesis and regional distribution of these tracers as currently practiced worldwide in the supply of 18F-fluorodeoxyglucose for routine clinical positron emission tomography (PET) imaging. 18F-florbetaben (FBB; trans-4-(N-methyl-amino)-4″(2-(2-(2-[18F] fluoro-ethoxy)ethoxy)-ethoxy)stilbene), developed by Avid Radiopharmaceuticals (Philadelphia, USA) and Bayer-Schering Pharma (Berlin, Germany), has been shown to bind with high affinity to A?? in brain homogenates and selectively labeled A?? plaques and cerebral amyloid angiopathy (CAA) in AD tissue sections [15].

After injection into Tg2576 transgenic mice, ex vivo brain sections showed localization of FBB in regions with A?? plaques as confirmed by thioflavin binding [16]. At the tracer concentrations achieved during human PET studies, FBB did not show binding to ??-synuclein in Lewy bodies or to tau lesions in postmortem cortices from dementia with Lewy bodies, AD or frontotemporal lobar degeneration patients [17]. In human studies, cortical retention of FBB was significantly higher in AD patients compared with age-matched controls and frontotemporal lobar degeneration patients, with binding matching the reported postmortem distribution of A?? plaques [9]. Phase II clinical studies further confirmed these results [8]. FBB is highly correlated with 11C-PiB (r = 0.97 GSK-3 with a slope of 0.

71) [18], free copy and was used to detect the presence or absence of AD pathology in the brain in participants with a wide spectrum of neurodegenerative diseases including a few MCI participants [10]. Phase III studies for FBB have reached completion [19]. Human postmortem studies have shown that while soluble A?? oligomers and the density of neurofibrillary tangles strongly correlate with neurodegeneration and cognitive deficits, the density of A?? insoluble plaques does not [20-24] and ???? burden as assessed by PET does not strongly correlate with cognitive impairment in AD patients [25,26].

After that, to analyse the data collected the VirtualDub 1 8 8 so

After that, to analyse the data collected the VirtualDub 1.8.8 software by Avery Lee was used. To obtain boat velocity information, the frame in which the bow of the kayak/canoe was aligned with the buoys was selected. These buoys indicated the beginning and the end of the sections analyzed. Then, the difference between the initial and final frame of each stage was calculated. selleck compound The time taken to cover the section was calculated by dividing this number by 30. Finally, boat velocity (m/s) was obtained dividing 50 m by the time taken to cover the section. Cycle frequency (cycles/s) was calculated by counting the complete cycles performed in the section. In this case, the frames when the blade tip first contacted the water were selected. These frames were always higher or equal to the number of frames used to calculate the velocity.

After that, the difference between the initial and the final frame was divided by 30. Then, the number of complete cycles was divided by this number. There were two additional circumstances taken into account in this analysis: 1) the first cycle of each race was excluded because the boat started from a static position, so this cycle was different to the rest; 2) to calculate the last cycle frequency, the frame when the blade tip last contacted the water surface before the finish line was used. The cycle length (m/cycle) of each section was calculated by dividing the kayak velocity between the cycle frequency obtained in a certain section. To calculate the cycle index (m2/(cycles?s)) the boat velocity was multiplied by the cycle length obtained in each section.

Analyses Data were analysed using the Statistical Package for Social Sciences (SPSS Inc, version 15.0, Chicago, ILL, USA) via repeated measures ANOVA and post hoc Bonferroni tests. Reliability and within-subject variability for mean and peak responses were assessed using intraclass correlation coefficients (ICC) and measures bias/ratio with associated 95% limits of agreement (LOA), respectively. Data are presented as mean �� SD with alpha set at 0.05. Results Boat velocity values for the four sections are shown in Table 1. What is worth mentioning is that boat velocity evolution was similar for all paddlers with a first section slower and a second section faster than the others. After that, the velocity decreased significantly (p<0.

05) in the two final sections, except in the last section of the men canoe test. There Cilengitide were significant differences (p<0.05) in men and women kayakers in the first section when compared with the others and among all groups comparing the second section with the 100 to 150 m section. Comparisons between the groups demonstrated significant differences in velocity (p<0.01) because men kayakers were the fastest in all sections. In addition, significant differences (p<0.01) were found between women kayakers and men canoeists in the 50 to 100 m and in the 100 to 150 m sections.

Ungerechts et al (1998) found that while the swimming velocity o

Ungerechts et al. (1998) found that while the swimming velocity of dolphins increases with kick frequency, amplitude and kick frequency selleck catalog are independent. Moreover, Hochtsein and Blickhan (2010) recently suggested that although the human body is limited by the asymmetry of its movement, it possesses as high flexibility as a body of a fish, allowing high-level swimmers to mimic the locomotion strategies of fish. They also discovered that several of the behaviours of aquatic animals could be mimicked to enhance the performance of swimmers. Over the years, researchers have sought to identify various technical indicators that can improve swimming performance. Accordingly, researchers have developed studies to produce relevant information that can help swimmers and coaches to apply practical decisions with regard to the technical model that is used.

Movement has commonly been regarded as comprising of sinusoids of a particular frequency and phase characteristics of the swimming stroke, generating the hypothesis that movement is controlled by ��oscillator-like mechanisms�� (Kelso et al., 1980; 1981). Thus, it is possible that an objective measure of the differences between movement patterns could be achieved by quantifying the fundamental waveforms and its frequency harmonics. The study of the cephalous – caudal wave was started by Sanders et al. (1995; 1998), who used Fourier analysis to quantify the amplitude and phase of the vertical undulations of butterfly stroke swimmers. Sanders et al. (1995) showed that the vertical displacement-time profiles of the body parts of skilled butterfly swimmers are characterised by low frequency waveforms.

These phase relationships result in a caudal wave traveling along the body during the stroke cycle. Sanders et al. (1998) also reported that the percentage of power contained in the fundamental frequency of the vertex, head and shoulder vertical undulations causes the swimmer to modify his technique from a conventional (flat) style to wave action. In other studies, the Strouhal number has been shown to be an indicator of efficiency that relates beat frequency and amplitude to swimming velocity (Triantafyllou and Triantafyllou, 1995; Fish and Ror, 1999; Arrelano et al., 2002). While there have been numerous recent reports about the breaststroke swimming technique, there has been a lack of detailed studies examining the wave motions in breaststroke with the use of equipment such as a snorkel.

The Aquatrainer? snorkel (K4 b2, Rome, Italy) allows the measurement of ventilation and oxygen uptake during swimming, and several studies have shown that this equipment recorded the cardiorespiratory parameters of swimmers with validity and accuracy (Toussaint et al., 1987; Keskinen et al., 2003; Rodriguez et al., 2008). Therefore, it is relevant to analyse the Anacetrapib effects of snorkel use and its contribution and suitability as a training device. Barbosa et al.

46; p=0 0001; Partial ?2=0 276), and BMI (F=12 57; p=0 0001;

46; p=0.0001; Partial ?2=0.276), and BMI (F=12.57; p=0.0001; add to your list Partial ?2=0.111) among the positions. The backs and line players were taller than other players. In addition, the measurement of body mass showed that the line players had the highest body mass and BMI values (Table 3). Table 3 Anthropometric characteristics of male handball players in the 2013 World Championship grouped according to their positions For further analysis of the data, the teams were divided into five groups according to their geographical location (Table 4). European players had significantly higher values in age, standing stature and body mass than the others. Table 4 Anthropometric characteristics of male handball players in the 2013 World Championship grouped according to their continents Furthermore, position-adjusted partial correlations showed that there were negative associations between the ranks of the teams and age (r = ?0.

150; p=0.002), standing stature (r = ?0.398; p=0.0001), and body mass (r = ?0.253; p=0.0001; Table 5). Table 5 Position-adjusted partial correlation coefficient among anthropometric measures and ranks of teams Discussion Previous reports have shown that body stature and morphological characteristics can determine the selection of participants in many sports (Hasan et al., 2007). To succeed in a sport discipline, it is often important to have specific anthropometric attributes (Ziv and Lidor, 2009). Handball involves frequent body contact and several high-intensity actions as part of a match play (P��voas et al., 2012).

Knowledge of the physical characteristics of handball players can provide insight into the individual factors which influence the players�� performance in the game (Hasan et al., 2007). The most striking comparison of anthropometric features of handball players in the present study was the difference in standing stature and body mass among the groups. Players in G1 had the highest standing stature and body mass when compared with players in G6, while BMI was not different across the groups (Table 2). In one study, elite (who were members of the current Spanish handball champions) and amateur handball players of the same age were compared. The elite players were taller, heavier and had a higher fat-free mass and higher BMI than the amateur players (Gorostiaga et al., 2005).

Marques and Gonzalez-Badillo (2006) reported the stature and body mass of the high-level team handball players were 184.2 �� 13.1 cm and 84.8 �� 13.1 kg, respectively (Marques and Gonzalez-Badillo, 2006). Marques et al. (2007) also reported the stature and body mass of the senior elite male team-handball players were 182.1 �� 6.7 cm and 82.5 �� 12.2 kg, respectively (Marques et al., 2007). However, the values of both studies were lower than players AV-951 in G6 of the present study. Lean mass, especially in the upper body, i.e. the body segment most involved in throwing, is the key feature of handball (Milanese et al., 2011).

001; 2 = 0 55), TTSA (p < 0 001; 2 = 0 50), FSA (p = 0 005; 2 = 0

001; 2 = 0.55), TTSA (p < 0.001; 2 = 0.50), FSA (p = 0.005; 2 = 0.47) and HSA (p < 0.001; 2 = 0.59). Quartile 1 had a higher BM, TTSA and FSA, followed by quartile 2, 4 and 3, respectively. H, AS and HSA decreased from quartile 1 to quartile 4. The selleck products interaction between gender and the sports level was non-significant for all selected variables, but with a moderate-strong effect. Figure 3 presents the kinematic variations based on the sports level and the interaction between gender and the performance level. Gender had a significant but minimum effect on the SF (p = 0.003; 2 = 0.12). Remaining variables showed non-significant effects (i.e. SL; dv and; v). SF was higher in boys than girls in quartile 2 (p = 0.02) and quartile 4 (p = 0.04). The sports level did not have a significant effect on the SF and dv, but did so on the SL (p < 0.

001; 2 = 0.32) and v (p < 0.001; 2 = 0.64). Both SL and v decreased from quartile 1 to quartile 4. The interaction between gender and the sports level was non-significant for all kinematic variables and a moderate-strong effect was observed. Figure 3 Mean data comparison by sports level, and by sports level according to gender of kinematic selected variables. SF �C stroke frequency; SL �C stroke length; dv �C speed fluctuation; V �C swimming velocity. Solid lines represent ... Figure 4 presents the energetic variations based on the sports level and interaction between gender and the sports level. There was a non-significant gender effect on the p, SI and CV. The sports level did not have a significant effect on p, but did so on SI (p < 0.

001; 2 = 0.55) and CV (p < 0.001; 2 = 0.46). Stroke index and CV were higher in quartile 1, and decreased up to quartile 4. The interaction between gender and the sports level was non-significant for p, SI and CV. Figure 4 Mean data comparison by sports level, and by sports level according to gender of energetic selected variables. ��p �C propulsive efficiency; SI �C stroke index; CV �C critical velocity. Solid lines represent p �� 0.05 ... Discussion The aim of this study was to analyze the gender and sports level effects on young swimmers�� anthropometrics, kinematics and energetics. Overall the data showed neither a gender effect nor gender versus sports level interaction. However, a sports level effect was reported. Present data shows that there is no gender gap comparing swimmers with the same sports level.

Although the high-level swimmers significantly differ from lower skilled ones. Faster swimmers are taller, with higher AS and surface areas, higher SL, v, SI and CV. These features are positively related to young swimmers�� performance (J��rim?e et al., 2007; Vitor and B?hme, 2010). Research with young swimmers is not as common as for adult/elite counterparts (e.g. Schnitzler et al., 2011). Literature clearly reports the anthropometric, kinematic and energetic influence on adult/elite swimmers�� performance. Such Carfilzomib relationships are not so evident in their younger counterparts.

Taken together, an unmet need clearly remains for identifying alt

Taken together, an unmet need clearly remains for identifying alternative immunosuppressive regimens that (1) maintain antirejection Glioma efficacy with substantially reduced CNI exposure; (2) optimize renal function, both short- and long-term, by minimizing CNI nephrotoxicity; (3) avoid or minimize CNI-associated adverse events; (4) reduce the recurrence of HCV and HCC; (5) reduce the occurrence of de novo posttransplant malignancies. The mammalian target of rapamycin (mTOR) inhibitors could potentially meet these criteria, in part because they allow the use of immunosuppressive regimens that include reduced doses of CNIs. The mTOR inhibitors also possess a mechanism of action that is different from other classes of immunosuppressants: sirolimus and everolimus engage FKBP12 to create complexes that engage and inhibit the target of rapamycin but cannot inhibit calcineurin (Figure 1).

Inhibition of the target of rapamycin blocks signal 3 by preventing cytokine receptors from activating the cell cycle [33]. In addition, mTOR inhibitors may promote tolerance through actions on regulatory T-cells and dendritic cells [34, 35]. Figure 1 Sites of action of immunosuppressive drugs (adapted from [33] with permission). Two mTOR inhibitors are currently approved for use in transplantation. Everolimus is approved by the FDA for renal and liver transplantation and by the EMA for renal, heart and liver transplantation (Certican and Zortress, Novartis Pharma AG; Basel, Switzerland) [36, 37].

Clinical experience with everolimus in liver transplantation is limited by the fact that it was only recently approved for liver transplantation and it was not approved for renal transplantation in the EU until 2003 and in the US until 2010. Sirolimus is approved by the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) for renal transplantation (Rapamune, Pfizer, NY, USA) [38, 39]. In the US, sirolimus was approved for renal transplantation in 1999. Although not approved for liver transplantation, it has still been used in several centres in liver transplant recipients. Everolimus is a derivative of sirolimus, differing by one extra hydroxyethyl group at position 40 [40]. In human studies, everolimus has a shorter half life (30 hours) compared to the 62 hours of sirolimus and a quicker time to steady state (4 days versus 6 days) [36, 38]. Both everolimus and sirolimus Drug_discovery are substrates in the p-glycoprotein and cytochrome P450-3A4 pathways [40, 41]. Therefore, the absorption and clearance of mTOR inhibitors may be influenced by drugs that affect cytochrome P450-3A4 and/or p-glycoprotein, including common drugs such as fluconazole, azithromycin, and protease inhibitors [36, 38, 39].