The prognosis for patients multiple myeloma (MM) has improved substantially over the past decade with the development of new, more effective chemotherapeutic agents and regimens that possess a high ...level of anti-tumor activity. In spite of this important progress, however, nearly all MM patients ultimately relapse, even those who experience a complete response to initial therapy. Management of relapsed MM thus represents a vital aspect of the overall care for patients with MM and a critical area of ongoing scientific and clinical research. This comprehensive manuscript from the International Myeloma Working Group provides detailed recommendations on management of relapsed disease, with sections dedicated to diagnostic evaluation, determinants of therapy, and general approach to patients with specific disease characteristics. In addition, the manuscript provides a summary of evidence from clinical trials that have significantly impacted the field, including those evaluating conventional dose therapies, as well as both autologous and allogeneic stem cell transplantation. Specific recommendations are offered for management of first and second relapse, relapsed and refractory disease, and both autologous and allogeneic transplant. Finally, perspective is provided regarding new agents and promising directions in management of relapsed MM.
Mycobacterium tuberculosis and filarial coinfection is highly prevalent, and the presence of a tissue-invasive helminth may modulate the predominant type 1 T helper (Th1; interferon IFN–γ–mediated) ...response needed to control M. tuberculosis infection. By analyzing the cellular responses to mycobacterial antigens in patients who had latent tuberculosis with or without filarial infection, we were able to demonstrate that filarial infection coincident with M. tuberculosis infection significantly diminishes M. tuberculosis–specific Th1 (interleukin IL–12 and IFN-γ) and type 17 T helper (Th17; IL-23 and IL-17) responses related to increased expression of cytotoxic T lymphocyte antigen (CTLA)–4 and programmed death (PD)–1. Blockade of CTLA-4 restored production of both IFN-γ and IL-17, whereas PD-1 blockade restored IFN-γ production only. Thus, coincident filarial infection exerted a profound inhibitory effect on protective mycobacteria-specific Th1 and Th17 responses in latent tuberculosis, suggesting a mechanism by which concomitant filarial (and other systemic helminth) infections predispose to the development of active tuberculosis in humans
Introduction: The relationship of tobacco use to dental caries is still unclear. The aim of this study is to assess the relationship between smoking and smokeless tobacco usage and prevalence of ...dental caries and its pattern in the Varanasi population. Materials and Methods: In this study, 472 elderly dentate and consenting individuals were included. Individuals were examined with the aid of mouth mirror, No. 23 explorer, and cotton rolls. The age of the study group ranged from 16 years to 75 years. Individuals were categorized as smoking tobacco users, smokeless tobacco users, and the combination of these two. Frequency and dosage of tobacco usage was recorded. Dental caries was measured using decayed, missing, and filled teeth (DMFT) index. Oral hygiene practices such as mode, material, and frequency of brushing were also recorded. Data were assessed using SPSS 17.0 using Chi-square, t-test, ANOVA test, and binary regression. Results: Caries rate was similar in both males and females (2.57 and 2.70), and the difference was not statistically significant. Caries was higher in individuals with habits when compared to those who were not having habits. There was no statistically significant association between individuals who were smokers, using smokeless tobacco, frequency, mode, and material of brushing with caries pattern. Among smokers, DMFT increased with frequency and duration of smoking, and it was statistically significant; however, in smokeless tobacco users, this was not the case. There was a positive correlation with DMFT and frequency of smoking. Conclusion: The study has shown that tobacco habit is a risk factor for increased caries activity, and it is higher in smokers as compared to smokeless tobacco chewers.
Background and Aims: Postoperative upper airway complications are frequently encountered with the use of supraglottic airway devices (SADs). Cuff pressure is one of the risk factors for upper airway ...complications with SADs. Among SADs, i-gel has shown lesser incidence. The effect of different cuff pressures on the incidence of postoperative upper airway complications is not known with Ambu AuraGain and nor has Ambu AuraGain been compared with i-gel in this regard. So, we undertook this study. Methods: A total of 200 patients undergoing elective laparoscopic surgery were randomised into 3 groups based on the SAD used and intra-cuff pressure: i-gel (IG) (n = 66); Ambu AuraGain at 25 cmH2O cuff pressure (AL) (n = 67); and Ambu AuraGain at 60 cmH2O cuff pressure (AH) (n = 67). The oropharyngeal leak pressures (OLPs) were measured after insertion and generation of carboperitoneum. An observer who was blind to the intraoperative details assessed the patients for two postoperative days for sore throat, dysphagia, dysphonia, or any other upper airway complications. Results: The OLPs before and after carboperitoneum in the 3 groups were (IG-24.22 ± 7.87 and 28.31 ± 8.52, AL-24.40 ± 5.84 and 26.94 ± 5.93, AH-25.02 ± 5.02 and 28.91 ± 5.6) cmH2O (P = 0.747 and P = 0.231). The overall incidence of postoperative sore throat among the 3 groups was: IG-5.7%, AL-14.9%, and AH-17.9%; P = 0.135. Dysphagia was seen only with Ambu AuraGain at high pressure in 4 patients (5.97%) (P = 0.017). Conclusion: Limiting cuff pressure in Ambu AuraGain to 25, as against 60 cmH2O, does not affect the OLP but has the potential of reducing the incidence of dysphagia.
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•Novel material was synthesized using carbon quantum dots (CQD) and nano zirconia.•ZrO2 nanoparticles with an average diameter of 40 nm were synthesized.•Carbon quantum dots were ...synthesized via calcining a solution of ammonium citrate.•Mixing in absolute ethanol was adopted for the formation of CQD-decorated ZrO2.•CQD decorated nano zirconia showed excellent photocatalytic effect.
A unique and efficient composite material was synthesized by incorporating carbon quantum dots on to the surface of zirconia (ZrO2) nanoparticles. ZrO2 nanoparticles with an average diameter of 40 nm were synthesized by a sol-gel process with zirconium oxychloride as the precursor. Carbon quantum dots (CQDs) were synthesized via a facile method by calcining a solution of ammonium citrate. Synthesized CQDs suspended in absolute ethanol emitted a green glow under UV irradiation. A convenient one-step process involving mixing in absolute ethanol under sonication was adopted for the formation of CQD-decorated ZrO2 nanoparticles (CQDZ). The dried final composite was characterized by scanning electron microscopy, transmission electron microscopy, X-ray diffraction and Fourier transform infrared (FT-IR) spectroscopy. The photocatalytic performance of CQDZ was evaluated by quantifying the removal efficiency of methylene blue dye. CQDZ managed to remove methylene blue by 66.5%, 76.5%, 84.3% and 95.0% under UV-irradiation of 10, 20, 40 and 60 min respectively. Under the same experimental conditions, pure ZrO2 nanoparticles managed to remove only 34% of the dye under 60 min of UV irradiation. The produced composite showed promise as a formidable contender to be used in industrial dye removal from waste water.
Adiponectin is an adipocyte-derived secretory factor that is specifically produced in adipocytes. It exerts effects on energy homeostasis via peripheral and central mechanisms. However, it is not ...clear whether adiponectin crosses the blood-brain barrier in humans. In serum, adiponectin circulates in several different complexes, each of which has distinct functions. Here, we wanted to test whether adiponectin can be found in human cerebrospinal fluid (CSF) and whether specific adiponectin complexes are enriched in CSF compared with peripheral serum samples. We also wanted to establish whether there is a sex-related difference with regard to the distribution of adiponectin oligomers in CSF.
We studied 22 subjects (11 men, 11 women) in this study. Their average BMI was 28.0+/-4.7 kg/m2; average age was 70+/-7 years.
Analysis of total adiponectin revealed that adiponectin protein is present in human CSF at approximately 0.1% of serum concentration. The distribution of adiponectin oligomers differs considerably in CSF from that of serum within matched samples from the same patients. Only the adiponectin trimeric and low-molecular-mass hexameric complexes are found in CSF, with a bias towards the trimeric form in most patients. Male subjects have a higher CSF:serum ratio of total adiponectin (p<0.05; n=20) and have slightly higher trimer levels in serum and CSF than female subjects.
We conclude that the adiponectin trimer is the predominant oligomer in human CSF.
Thin films of Poly 3-hexylthiophene (P3HT) were deposited onto Indium Tin Oxide (ITO) coated glass substrates using a spin coating method and the films were vacuum annealed at different temperatures ...to study the effect of annealing on the electrochemical reversibility. From the absorption spectra, the variation of the optical band gap with annealing temperature was studied for different annealing temperatures. The optical band gap obtained for P3HT film deposited at room temperature (RT) was around 1.94 eV and 1.92 eV for the sample annealed at 100 °C. A cyclic voltammetry (CV) analysis showed that at certain applied redox potentials, P3HT thin films changed the colour from magenta to transparent and then back to magenta in the reverse potential. P3HT films annealed at 100 °C showed the best electrochemical reversibility among all the annealed samples. These electrically switchable electrochromic P3HT thin films can be used in flexible dynamic windows (FDWs) as smart windows for controlling the temperature and light in buildings, displays and mirror light modulators.
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•Effect of vacuum annealing temperature on the electrochemical reversibility of P3HT was studied.•An increase of around 24 % was obtained for the electrochemical reversibility of P3HT on annealing.•Enhanced electrochromic device performance was observed for annealed P3HT films.
Candida bloodstream infection, i.e. candidemia, is the most frequently encountered life-threatening fungal infection worldwide, with mortality rates up to almost 50%. In the majority of candidemia ...cases, Candida albicans is responsible. Worryingly, a global increase in the number of patients who are susceptible to infection (e.g. immunocompromised patients), has led to a rise in the incidence of candidemia in the last few decades. Therefore, a better understanding of the anti-Candida host response is essential to overcome this poor prognosis and to lower disease incidence. Here, we integrated genome-wide association studies with bulk and single-cell transcriptomic analyses of immune cells stimulated with Candida albicans to further our understanding of the anti-Candida host response. We show that differential expression analysis upon Candida stimulation in single-cell expression data can reveal the important cell types involved in the host response against Candida. This confirmed the known major role of monocytes, but more interestingly, also uncovered an important role for NK cells. Moreover, combining the power of bulk RNA-seq with the high resolution of single-cell RNA-seq data led to the identification of 27 Candida-response QTLs and revealed the cell types potentially involved herein. Integration of these response QTLs with a GWAS on candidemia susceptibility uncovered a potential new role for LY86 in candidemia susceptibility. Finally, experimental follow-up confirmed that LY86 knockdown results in reduced monocyte migration towards the chemokine MCP-1, thereby implying that this reduced migration may underlie the increased susceptibility to candidemia. Altogether, our integrative systems genetics approach identifies previously unknown mechanisms underlying the immune response to Candida infection.
Interannual climate modes, especially the southern annular mode (SAM), significantly influence the wave climate modulation of the Indian Ocean (IO). The present study, aligned with previous research, ...identifies two crucial swell generation regions in the IO: the extratropical southern Indian Ocean (ETSI) and the tropical southern Indian Ocean (TSIO). The SAM, governing Southern Ocean surface winds, significantly shapes wave generation in these zones, thereby dominantly regulating IO wave conditions. Positive SAM phases shifts the westerlies poleward creating significant negative anomalies in the northern ETSI, reducing wave generation and swell propagation into the northern IO (NIO) basins, while the positive wind anomalies in the western TSIO creates a new swell generation area that directs swells towards the Arabian Sea, elevating wave heights there during monsoons. Conversely, negative SAM phases enhance TSIO easterlies, making it the primary IO swell source, increasing swell activity in the Bay of Bengal, notably during premonsoon and monsoon seasons. SAM impact expands beyond swells, influencing NIO wave climate by altering wind seas through Hadley cell (HC) circulation shifts. Positive SAM phases trigger NIO and midlatitude anomalous warming, intensifying HC and NIO surface winds in the next season, thereby affecting convection and subsequent sea surface temperature (SST) anomaly changes. The “SAM positive anomaly wind‐SST oscillations (SPAWSO)” pattern emerges, where warm SST anomalies in DJF and JJA precede increased surface winds in MAM and SON, thus increasing the wind‐sea conditions in the NIO. SPAWSO, hence, acts as a delayed mode, season‐dependent positive air–sea interaction cycle linked to positive SAM phases, significantly impacting NIO's wind‐sea dynamics. Thus the present study provides better insights into the long‐term wave prediction accuracy in the IO by considering the direct swell influence and SPAWSO‐driven wind‐sea changes, aiding preparations for changing wave dynamics and their impacts.
Southern annular mode (SAM) induces an anomalous cooling in the extratropics and warming in the midlatitudes. The temperature gradient strengthens during SAM positive phase and enhances the poleward expansion of the Hadley cell which weakens the wind over the Indian Ocean (IO). The weak winds over IO causes a decrease in wave height especially the north IO.
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