Coronary Artery Disease in Patients ≥80 Years of Age

Coronary artery disease (CAD) is a major cause of morbidity and mortality in patients ≥80 years of age. Nonetheless, older patients have typically been under-represented in cardiovascular clinical trials. Understanding the pathophysiology, epidemiology, and optimal means of diagnosis and treatment of CAD in older adults is crucial to improving outcomes in this high-risk population. A patient-centered approach, taking into account health status, functional ability and frailty, cognitive skills, and patient preferences is essential when caring for older adults with CAD. The present systematic review focuses on the current knowledge base, gaps in understanding, and directions for future investigation pertaining to CAD in patients ≥80 years of age.     

Prognostic importance of DNA repair gene polymorphisms of <Emphasis Type="Italic">XRCC1</Emphasis> Arg399Gln and <Emphasis Type="Italic">XPD</Emphasis> Lys751Gln in lung cancer patients from India

Purpose Inter individual variation in lung cancer susceptibility may be modulated in part through genetic polymorphisms in the DNA repair genes, especially the genes involved in the Base Excision Repair (BER) and nucleotide excision repair (NER) pathway. Two of the genetic polymorphisms, XRCC1Arg399Gln and XPD Lys751Gln have been extensively studied in the association with lung cancer risk, although published studies have been inconclusive. Methods In order to verify the role of the common variant alleles in the XPD gene, we have genotyped 211 lung cancer patients and 211 healthy controls using PCR-RFLP assays in a hospital based, case-control study in an Indian population. Logistic regression models were fit to examine the relationship between the log odds of lung cancer and each covariate. Overall Survival in relation to various genotypes and clinicopathological factors were analyzed using Kaplan Meier estimates and hazard ratios were calculated using Cox Regression analysis. Results The carriers of XRCC1 399 AA genotypes were at higher risk of lung cancer (OR = 2.1, 95% CI:1.224–3.669, P = 0.007) than carriers of GG genotype. Subjects carrying 751 AC genotype were at an increased risk of carcinoma of the lung (OR = 1.8; 95% CI:1.233–2.807, P = 0.003) than subjects with AA genotypes. Compared to the XRCC1 399 GG/ XPD 751 AA reference genotype, the combined variants, XRCC1 399 GG/ XPD 751 AC+CC (OR = 1.9, 95% CI: 1.037–3.481), P = 0.03), XRCC1 399 GA+AA/ XPD 751 AA (OR = 1.7, 95% CI: 1.020–2.833, P = 0.04), XRCC1 399 GA+AA/XPD 751 AC+CC (OR = 2.7, 95% CI: 1.582–4.864, P = 0.01), had significantly higher odds ratios. Increasing numbers of either XPD or XRCC1 variant alleles were associated with shorter overall survival, the risk being significant for the XRCC1 gene polymorphism (P = 0.01 by log-rank test). The hazard of dying was significant for the XRCC1 399 AA genotype (HR = 3.04, 95%CI: 1.393–6.670, P = 0.005). Higher tumour stage also came out as significant predictors of patient death. Conclusions These findings suggest that genetic polymorphisms in the DNA repair genes may modulate overall lung cancer susceptibility and that pathological stage and XRCC1 Arg399Gln independently predicted overall survival among Indian lung cancer patients.     

IoT-enabled dye-sensitized solar cells: an effective embedded tool for monitoring the outdoor device performance

Herein, we have developed a tool for monitoring the outdoor performance of dye-sensitized solar cells. In this regard, a new dye consisting of an N-aryl-substituted imidazole with N-alkylated carbazole as the donor and cyanoacrylic acid as the acceptor has been designed. The overall power conversion efficiency of the designed dye reached ∼50%, with respect to that of the N719-based device (4%) under similar experimental conditions. Further, the device was interfaced with an IoT system, which measured the voltage and transmitted the device parameters to the user''s mobile phone through a cloud channel. The developed IoT tool provides a resolution of 0.0315 mV and a round-trip delay time of <0.32 s for transmitting the information to the user''s mobile phone.

Herein, we have developed a tool for monitoring the outdoor performance of dye-sensitized solar cells.

Since the discovery of the first web-connected appliance in 1990, the Internet of Things (IoT) has received considerable attention.¹ The IoT is a megatrend in technology that covers the entire scientific and engineering disciplines besides internet technology-affiliated communities. The IoT devices are perceived to be power efficient and small in size making them portable, and hence capable of operating in battlefields, agricultural fields, healthcare, transportation, roof top monitoring and even seismic event monitoring.² The mode of communication can be wired or wireless, based on the need of the user, but mostly it is wireless in nature. The wireless mode creates easy mobility to the users and provides data hand to hand. The IoT devices are equipped with wireless connection facilities such as IEEE 802.11 (Wireless fidelity), IEEE 802.15.4 (Zigbee) and IEEE 802.15 (Bluetooth) protocols. These protocols help in communicating the data to the desired remote location and the data collection in many cases are cloud-interfaced. The development of IoT assures deployment of sensor networks, which obtain real-time data from the sensor nodes across the on-site areas. This design has been successfully demonstrated for water supply and management.^3–5 However, numerous challenges with respect to data collection/communication/storage and device power exist, and should be overcome to make this technology suitable for practical applications. Apart from water supply and management, the IoT concept is all set for chemical and bio-sensing applications.⁶ For instance, Yao and later Liao et al. demonstrated a tear fluid detection with wireless transmission using a contact lens-integrated amperometric glucose biosensor. Very recently, Freitag et al. demonstrated a dye-sensitized photovoltaic device as a power source for the IoT and concluded that this concept is set to define technology for the ensuing decades.⁷In this context, our main motivation was to monitor the outdoor performance of a dye-sensitized photovoltaic device.^8–12 Consequently, we have interfaced the IoT to a dye-sensitized device fabricated using the newly synthesized dye molecule. The dye consists of an N-aryl-substituted imidazole with N-alkylated carbazole as the donor and cyanoacrylic acid as the acceptor/anchoring group (Scheme 1). The characterization results are provided in the ESI (Fig. S1–S5).^† The photophysical, electrochemical and photovoltaic properties were comprehensively investigated and the obtained results are discussed. Furthermore, the real-time V_OC characteristics of the device with respect to the input solar luminance were also monitored through the designed IoT module. The device was connected with a highly resistive A/D converter for recording the V_OC characteristics. In addition, the round-trip delay of the near real-time monitoring was also investigated for the firebase cloud interface.Open in a separate windowScheme 1Synthetic pathway of the ICA dye (3).The efficient light harvesting and charge separation in the dye-sensitized semiconductor system depends on the proficient charge transfer from the donor to the acceptor unit of the dye. Hence, UV-visible absorption spectral measurements have been carried out to understand the light harvesting and type of transition type of the ICA dye. The absorption spectrum of the ICA dye was recorded in the THF solvent and is depicted in Fig. 1a. The absorption spectrum of the ICA dye consists of two major absorption peaks (maxima) in the range of 250–500 nm. Typically, the band located between 250 and 350 nm is assigned to the π–π* transition, whereas the band situated in the range of 360–460 nm corresponds to the intramolecular charge transfer (ICT) transition. Among the two types of transitions in the ICA dye, the ICT transition is considered the favourable channel for DSCs. Hence, a detailed investigation on the ICT transition is necessary before employing the ICA dye for TiO₂ sensitization and photovoltaic measurements. Initially, the ICT character of the ICA dye was examined through DFT calculations. The time-dependent density functional theory (TDDFT) calculations with different functionals (B3LYP, CAM-B3LYP, M06, Wb97x, M06-2x and PBE0) were employed to find the best fit of experimental absorption with the theoretical data (Table S1^†). Among the various functionals, B3LYP revealed the best fit to the experimental λ_max value; hence, calculations were performed using the B3LYP functional. The computed optimized geometry of the ICA dye is displayed in inset of Fig. 1a. From the figure, it is apparent that the carbazole and cyanoacrylic acid units in the ICA dye are planar, while the imidazole unit is twisted by approximately 147° from the plane. This twisted structure can be clearly visualized from the side view of the optimized geometry (Fig. S6^†). The twisted structure generally enables the efficient intramolecular charge transfer (ICT) within the dye molecule. Thus, it is believed that the ICA dye has an ICT character during light excitation. This could be easily reorganized through the frontier molecular orbitals (FMOs) of the ICA dye. Fig. 1b and c portray the computed FMOs of the ICA dye and it can be seen that the electron density of the ICA dye in the HOMO is localized mainly on the donor moiety, while the LUMO is populated with the acceptor unit. The FMO picture unambiguously divulges the ICT character of the ICA dye. Further, the molecular electrostatic potential (MESP) map has also been computed to understand the ICT nature of the ICA dye (++). The region around the imidazole unit was found to be nucleophilic with an electrostatic potential of −30.00 kcal mol⁻¹ and the region in the vicinity of C O and C N in cyanoacrylic acid exhibited a potential of −28.35 kcal mol⁻¹ and −39.53 kcal mol⁻¹, respectively. The only electrophilic site in the molecule was around the –OH group of carboxylic acid with an electrostatic energy of +37.65 kcal mol⁻¹. Thus, the MESP map also endorsed the ICT character of the ICA dye.Open in a separate windowFig. 1(a) Absorption spectrum of ICA dye, inset shows the optimized geometry, (b) HOMO, (c) LUMO and (d) MESP of ICA dye.Generally, the energy levels such as HOMO and LUMO of a dye are vital to understand the electron transfer characteristics towards the TiO₂ conduction band. Therefore, cyclic voltammetry (CV) and differential pulse voltammetric (DPV) techniques were employed to locate the energy levels by measuring the redox potential of the dye. Fig. S7^† shows the CV and DPV voltammograms of the ICA dye in the THF solvent. From the CV plot, it can be observed that there is a sharp signal at the positive potential in the range of +0.5–0.6 V vs. Ag/AgCl and the precise value of oxidation potential is acquired from the DPV plot, which shows the value of +0.62 V vs. Ag/AgCl. This clearly suggests that the ICA dye undergoes a one-electron oxidation process. Notably, even after three cycles of CV, the signal was unaltered, which proves the electrochemical stability of the ICA dye under the applied potential. The energy of HOMO with respect to the oxidation potential of the ICA dye was calculated as −5.63 eV and was found to be lower than that of the redox potential of the iodine/iodide electrolyte (−4.8 eV). This value facilitates the efficient regeneration of the ICA molecule after the injection of its electron to the TiO₂ semiconductor. The absorption edge of the ICA dye was used to calculate the onset energy (E_onset) and was found to be 2.72 eV. Both HOMO and E_onset values were used to calculate the energy of LUMO and it was observed that LUMO (−2.91 eV) of the ICA dye was more negative than the conduction band of TiO₂ (−4.0 eV). This definitely favours the effective electron injection from the excited ICA dye to the conduction band of TiO₂. Thus, ICA dye can be a promising material for the construction of the photoanode in the DSC device.Sensitizing the TiO₂ semiconductor with a dye was the key step to develop the photoanode for DSC fabrication. A primary process in the photoanode upon photoexcitation is the electron injection and this process entirely depends on the dye binding as well as light harvesting properties of the material. In order to understand such properties of ICA on the TiO₂ surface, ∼4 micron thickness TiO₂ films were prepared from a commercially available titania paste (Solaronix SA, Ti-Nanoxide HT/SC series). The films were sensitized in 0.3 mM ICA dye in THF solvent at room temperature for 1 h. The normalized absorption spectrum of ICA-anchored TiO₂ thin film is displayed in Fig. 2a. As compared to the solution absorption spectrum, the ICA dye showed broad absorption with a bathochromic shift, which is typically due to the J-type aggregation of the dye.¹³ This would be beneficial to enhance the light harvesting efficiency of the ICA dye on the TiO₂ surface. However, the absorption spectrum of ICA on TiO₂ got blue shifted at lower concentration (0.03 mM). The observed blue shift was perhaps due to the H-aggregation or deprotonation of the carboxylic group. To establish whether the blue shift in the absorption spectrum is due to aggregation or deprotonation, we have compared the absorption spectra of 0.03 mM ICA/TiO₂ and ICA in triethylamine (TEA). The main intention of introducing TEA to the solution of ICA dye was to deprotonate carboxylic acid,^14,15 and as a result, it would weaken the electron-pulling strength of the acceptor moiety (–C N), which in turn may alter the ICT band of the ICA dye. Fig. 2a clearly shows that the absorption maxima of 0.03 mM ICA/TiO₂ and ICA/TEA are identical, and this confirms that the blue shift in the absorption spectrum is due to the deprotonation of the carboxylic group and not due to aggregation. Further, the constructed LHE spectra of the ICA-sensitized TiO₂ films in two different concentrations are shown in Fig. 2b. The calculated Γ values were 3.45 × 10⁻⁸ and 2.49 × 10⁻⁸ mol cm⁻² for high and low ICA dye concentrations, respectively. Based on the results, high concentration of ICA dye exhibited notable LHE (90%) and Γ values. Thus, a high concentration of ICA dye is recommended for photovoltaic applications.Open in a separate windowFig. 2(a) Normalized absorption spectra of ICA in TEA and titania surface, (b) LHE spectra of ICA-sensitized TiO₂ films.The LHE of ICA in the region from 400 nm to 520 nm, indicated that the ICA-sensitized TiO₂ device would generate the photocurrent. Hence, the photocurrent density–photovoltage (J–V) curve measurement was performed under simulated AM 1.5 solar irradiation (100 mW cm⁻²) and is shown in Fig. 3. The complete device fabrication details are given in the ESIn.^† The photovoltaic parameters of the ICA device are summarized in Table S2.^† The device based on the ICA dye shows an efficiency of 2.04%, with a short-circuit photocurrent density (J_SC) of 5.26 mA cm⁻², an open-circuit photovoltage (V_OC) of 0.58 V, and a fill factor (FF) of 0.66. For a fair comparison, the N719-sensitized DSC was also fabricated under the same conditions and yielded an η value of 4%. Conspicuously, the overall conversion efficiency of the ICA dye reached 51% with respect to the N719 dye. The efficacy of the ICA dye is also compared with previously reported carbazole derivatives^16–18 (Table S3^†). Further, structural optimization such as expanding absorption spectra to include more of the visible region and tuning HOMO/LUMO energy levels are expected to produce more efficient carbazole dyes and this work has commenced in our laboratory.Open in a separate windowFig. 3 J–V characteristics of ICA and ICA + CDCA.Further, to improve the performance of the ICA device, chenodeoxycholic acid (CDCA) was considered as a co-adsorbent. Since CDCA can anchor strongly to the TiO₂ surface, it would hinder the dye–dye interaction/aggregation.¹⁹ Thus, the performance of the ICA device in the presence of CDCA was studied. The results are presented in Table S2,^† and the corresponding J–V curve is shown in Fig. 3. Contrarily, CDCA did not play a vital role in device performance; however, the J_sc of the device decreased. To address the cause of difference in J_sc, we conducted surface coverage measurements of the ICA dye with and without CDCA. The Γ values were calculated to be 3.45 × 10⁻⁸ and 2.83 × 10⁻⁸ mol cm⁻² without and with CDCA, respectively. These values indicate that the amount of ICA dye adsorbed on the TiO₂ surface was reduced with the presence of CDCA, resulting in the loss of active light harvesting, in-turn suggesting that CDCA was not suitable for improving the performance. These results hint that the ICA dye did not aggregate on the TiO₂ surface.²⁰To further understand the charge transfer properties of the ICA device, a typical electrochemical impedance spectroscopy (EIS) analysis was employed. Fig. 4 shows the EIS Nyquist plot of ICA and ICA + CDCA devices. Nyquist plots have two semicircles. The first semicircle is generally attributed to the charge transfer resistance at the counter electrode/electrolyte interface, while the second semicircle in the middle-frequency range represents the charge-transfer resistance at the TiO₂/dye/electrolyte interface.²¹Open in a separate windowFig. 4(a) Nyquist and (b) Bode plots of ICA and ICA + CDCA devices.It can be seen from Fig. 4a that the radius of the larger semicircle increases a bit in the order of ICA + CDCA > ICA, indicating that the charge recombination resistance increased from ICA to ICA + CDCA. This is to some extent consistent with the order of V_OC: ICA + CDCA (0.59 V) > ICA (0.58 V). However, the difference in V_OC is not significant. A Bode phase plot is also related to the charge transfer resistance at the TiO₂/dye/electrolyte interface. Hence, the EIS Bode plots of the devices were also investigated (Fig. 4b). It is known that the reciprocal of electron lifetime is associated with the charge recombination rate, which in-turn is associated to the lower frequency peak in the Bode plot. Thus, the electron lifetime (τ_n) can be estimated from τ = 1/(2πf) where τ is the lifetime of electrons in TiO₂ and f is the frequency of the peak in the Bode plot. The calculated values were 98.91 and 97.75 ms for ICA and ICA + CDCA, respectively. Thus, EIS results indicate that the introduction of CDCA to ICA dye could not improve the V_OC. These results are in good agreement with the photovoltaic results.Further, to understand the outdoor performance of the developed dye-sensitized solar cells (DSSCs), we have employed the IoT technology. As is known, exposing the dye-sensitized photovoltaic device to sun light induces electron flow across the terminals. The terminals were connected in a very high resistance circuit (with voltage comparator or analog to digital circuit). The electron flow from the device pass through a very high resistance digital voltmeter (ADC converter), which has the capability to measure the voltage drop across the terminals at the mV level. The ADS1115 IC was connected with the microcomputer that has cloud connection capability and wireless fidelity modules. The microcomputer (i.e. Raspberry Pi Zero W processor) was programmed to measure the voltage across the terminal every second and update the same in the cloud repository. The cloud repository we have used is firebase. The round-trip delay between sensing and reporting to the android application was observed to be less than 0.33 s. The ADS1115 and the Raspberry Pi W IoT setup was powered with a battery setup to work indigenously throughout the monitoring session. Fig. 5a shows the IoT setup for monitoring the open circuit voltage of the device. The end terminal of the device was connected with the Analog to Digital Converter IC–ADS1115 with a gain factor of 1. The ADS1115 IC used in this setup was a 16 bit A/D converter with a resolution of 0.0315 mV. The ADS1115 IC was connected with the microcomputer (Raspberry Pi device) for the cloud interface through a Wifi support. The Raspberry Pi microcomputer was programmed to send the V_OC to the cloud interface and the same was viewed in the android-based application. Fig. S8^† illustrates the android application window displaying the live data from the device through cloud interface. The live streaming was done through the node-red programming language. Fig. 5b shows the V_OC monitored through the IoT interface from 09:00 to 17:00 h. The V_OC was observed to be maximum during peak day time 11.00 am to 02.00 pm.Open in a separate windowFig. 5(a) IoT setup (b) an output plot of V_OCvs. time in h. In (a) A, B and C indicate the Analog to Digital Converter IC – ADS1115 16 bit, Raspberry Pi microcomputer and battery power for the microcomputer, respectively.In summary, we have demonstrated the outdoor DSSC performance through the IoT technology. The designed IoT system effectively monitored the device performance through a cloud interface. The performance of the device was notified to the user through a mobile android application within 0.32 s. The round-trip time of the cloud interface shows effective communication establishment. The system provides a near real-time data on the performance of DSSCs.     

Biological evaluation of intervertebral disc cells in different formulations of gellan gum‐based hydrogels

Gellan gum (GG)‐based hydrogels are advantageous in tissue engineering not only due to their ability to retain large quantities of water and provide a similar environment to that of natural extracellular matrix (ECM), but also because they can gelify in situ in seconds. Their mechanical properties can be fine‐tuned to mimic natural tissues such as the nucleus pulposus (NP). This study produced different formulations of GG hydrogels by mixing varying amounts of methacrylated (GG‐MA) and high‐acyl gellan gums (HA‐GG) for applications as acellular and cellular NP substitutes. The hydrogels were physicochemically characterized by dynamic mechanical analysis. Degradation and swelling abilities were assessed by soaking in a phosphate buffered saline solution for up to 170 h. Results showed that as HA‐GG content increased, the modulus of the hydrogels decreased. Moreover, increases in HA‐GG content induced greater weight loss in the GG‐MA/HA‐GG formulation compared to GG‐MA hydrogel. Potential cytotoxicity of the hydrogel was assessed by culturing rabbit NP cells up to 7 days. An MTS assay was performed by seeding rabbit NP cells onto the surface of 3D hydrogel disc formulations. Viability of rabbit NP cells encapsulated within the different hydrogel formulations was also evaluated by Calcein‐AM and ATP assays. Results showed that tunable GG‐MA/HA‐GG hydrogels were non‐cytotoxic and supported viability of rabbit NP cells. Copyright © 2012 John Wiley & Sons, Ltd.     

Towards nanomedicines for neuroAIDS

Although highly active antiretroviral therapy (HAART) has resulted in remarkable decline in the morbidity and mortality in AIDS patients, controlling HIV infections still remain a global health priority. HIV access to the CNS serves as the natural viral preserve because most antiretroviral (ARV) drugs possess inadequate or zero delivery across the brain barriers. Thus, development of target‐specific, effective, safe, and controllable drug‐delivery approach is an important health priority for global elimination of AIDS progression. Emergence of nanotechnology in medicine has shown exciting prospect for development of novel drug delivery systems to administer the desired therapeutic levels of ARV drugs in the CNS. Neuron‐resuscitating and/or antidependence agents may also be delivered in the brain through nanocarriers to countercheck the rate of neuronal degradation during HIV infection. Several nanovehicles such as liposomes, dendrimers, polymeric nanoparticles, micelles, and solid lipid nanoparticles have been intensively explored. Recently, magnetic nanoparticles and monocytes/macrophages have also been used as carrier to improve the delivery of nanoformulated ARV drugs across the blood–brain barrier. Nevertheless, more rigorous research homework has to be elucidated to sort out the shortcomings that affect the target specificity, delivery, release, and/or bioavailability of desired amount of drugs for treatment of neuroAIDS. Copyright © 2014 John Wiley & Sons, Ltd.     

Diabetes and orthopaedic surgery: a review

Diabetes mellitus (DM) is common, estimated to affect 425 million people worldwide in 2017. It is a condition that is continually growing in prevalence and is often associated with multiple co-morbidities. Its multi-system effects on the body mean that its management can pose a challenge, even to more experienced clinicians. In orthopaedic practice, diabetic patients are commonly encountered owing to their increased fracture risk and complications of the disease such as diabetic foot. An appropriate knowledge of diabetes, its pathophysiology, immunology and the pharmacology of medications used in its treatment is essential, as the consequences of mismanagement can be grave. Optimal treatment of diabetics can often require the involvement of a wider multidisciplinary team. Complications that can be encountered in the perioperative and postoperative periods include, diabetic ketoacidosis, hyperosmolar hyperglycaemic state, surgical site infection and venous thromboembolism. This review outlines current concepts in the perioperative management of diabetes and its manifestations within orthopaedic surgery, with a focus on outcomes and complications. A review of the available literature reveals conflicting conclusions between studies, with no clear effect or consensus yet established for many issues. There is a need for a greater number of well-designed, high-quality, appropriately powered trials to establish the true effect of diabetes on outcomes in orthopaedic surgery.     

Mosquitoes survive raindrop collisions by virtue of their low mass

In the study of insect flight, adaptations to complex flight conditions such as wind and rain are poorly understood. Mosquitoes thrive in areas of high humidity and rainfall, in which raindrops can weigh more than 50 times a mosquito. In this combined experimental and theoretical study, we here show that free-flying mosquitoes can survive the high-speed impact of falling raindrops. High-speed videography of those impacts reveals a mechanism for survival: A mosquito's strong exoskeleton and low mass renders it impervious to falling drops. The mosquito's low mass causes raindrops to lose little momentum upon impact and so impart correspondingly low forces to the mosquitoes. Our findings demonstrate that small fliers are robust to in-flight perturbations.