Health-related quality of life and its determinants among cancer patients: evidence from 12,148 patients of Indian database.

BACKGROUND: Cancer survivors experience a decrement in health-related quality of life (HRQoL) resulting from the disease as well as adverse effects of therapy. We evaluated the HRQoL of cancer patients, stratified by primary cancer site, stage, treatment response and associated adverse events, along with its determinants. METHODS: Data were collected from 12,148 patients, sampled from seven purposively chosen leading cancer hospitals in India, to elicit HRQoL using the EuroQol questionnaire comprising of 5-dimensions and 5-levels (EQ-5D-5L). Multiple linear regression was used to determine the association between HRQoL and various socio-demographic as well as clinical characteristics. RESULTS: Majority outpatients (78.4%) and inpatients (81.2%) had solid cancers. The disease was found to be more prevalent among outpatients (37.5%) and inpatients (40.5%) aged 45-60 years and females (49.3-58.3%). Most patients were found to be in stage III (40-40.6%) or stage IV (29.4-37.3%) at the time of recruitment. The mean EQ-5D-5 L utility score was significantly higher among outpatients [0.630 (95% CI: 0.623, 0.637)] as compared to inpatients [0.553 (95% CI: 0.539, 0.567)]. The HRQoL decreased with advancing cancer stage among both inpatients and outpatients, respectively [stage IV: (0.516 & 0.557); stage III (0.609 & 0.689); stage II (0.677 & 0.713); stage I (0.638 & 0.748), p value < 0.001]. The outpatients on hormone therapy (B = 0.076) showed significantly better HRQoL in comparison to patients on chemotherapy. However, palliative care (B=-0.137) and surgery (B=-0.110) were found to be associated with significantly with poorer HRQoL paralleled to chemotherapy. The utility scores among outpatients ranged from 0.305 (bone cancer) to 0.782 (Leukemia). Among hospitalized cases, the utility score was lowest for multiple myeloma (0.255) and highest for testicular cancer (0.771). CONCLUSION: Older age, lower educational status, chemotherapy, palliative care and surgery, advanced cancer stage and progressive disease were associated with poor HRQoL. Our study findings will be useful in optimising patient care, formulating individualized treatment plan, improving compliance and follow-up.

Daratumumab in Indian patients with relapsed and refractory multiple myeloma: a prospective, multicenter, phase IV study.

Aim: To assess the safety and effectiveness of daratumumab monotherapy in Indian patients with relapsed/refractory multiple myeloma. Methods: In this prospective, multicenter, phase IV study, patients (aged ≥18 years) received intravenous daratumumab (16 mg/kg) in six cycles. Safety was the primary end point. Results: Of the 139 patients included, 121 (87.1%) experienced ≥1 treatment-emergent adverse events (TEAEs; 53 [38.1%] drug-related), 32 (23%) had ≥1 serious TEAEs (five [3.6%] drug-related) and 16 (11.5%) deaths were reported (one death [0.7%] was drug-related). Overall response rate was 26.3%; 62.7% of patients had stable disease. Median time to first response and median progression-free survival were 5.2 and 5.9 months, respectively. Functional status and well-being were improved. Conclusion: Daratumumab showed an acceptable and expected safety profile with consistent efficacy, providing a novel therapeutic option for relapsed/refractory multiple myeloma management in India.

Daratumumab is a monoclonal antibody approved for the treatment of patients with relapsed/refractory multiple myeloma (RRMM). This study evaluated the outcome of daratumumab single therapy in Indian patients who were not cured with other drugs used for the same disease. 139 adult patients were included in this study from 15 institutes across India. Daratumumab (16 mg/kg) was diluted with 500 or 1000 ml of saline solution and given slowly through the intravenous route 16-times within 6 months. The study examined whether the safety profile and benefits of daratumumab reported in Indian patients were similar to those reported in the RRMM populations of other countries. The study found that most of the adverse events were not severe and could be easily treated by the study physician. 16 patients died (one might have been due to daratumumab treatment). Daratumumab treatment provided life support and recovery benefits to many patients. Daratumumab single therapy provides an appropriate and acceptable safety profile with no new adverse events and consistent benefits in RRMM patients. Clinical Trial Registration: NCT03768960 (ClinicalTrials.gov), CTRI/2019/06/019546.

Quality of life and symptom burden in hematological cancer patients receiving hematopoietic stem cell transplantation: an observational study at Regional Cancer Centre, India.

PURPOSE: Hematopoietic stem cell transplant (HSCT) is an intense form of treatment, resulting in major symptom burden but can prove curative. The quality of life (QOL) is a major endpoint for these patients as the survival rate in them has improved over time. The aim of the study is to assess the QOL and symptom burden of hematological malignancy patients at admission to hospital for HSCT, at 1 month and at 3 months following HSCT. METHODS: This prospective observational study was done on hematological malignancy patients who were admitted for HSCT in a regional cancer center. The study subjects were assessed by the Functional Assessment of Cancer Therapy-Bone Marrow Transplant Scale (FACT-BMT Scale), Edmonton Symptom Assessment Scale-revised (r-ESAS), and Depression, Anxiety and Stress Scale-21 Items (DASS-21) at the time of hospital admission for transplantation, on day 30 (~ 1 month) and day100 (~ 3 months) of transplantation. RESULTS: A total of 68 patients were included in this study. FACT-BMT scores have decreased from baseline (F0) to the first follow-up (F1) and then increased in the third follow-up (F2). The maximum r-ESAS mean score was for tiredness among all other symptoms at F0 as well as at F1 and at F2. The DASS 21 scores for depression, anxiety, and stress were maximum during F1 and minimum during F2. CONCLUSION: Symptom burden is maximum during the first month of BMT, which improves later and QOL becomes improved with time.

Primary Mediastinal Germ Cell Tumors (PMGCT): A Real-world Analysis From A Tertiary Cancer Care Center in India.

BACKGROUND: Primary mediastinal GCT (PMGCT) is a rare entity and comprises 10-15% of all mediastinal tumors. We present our institutional experience of MGCT treated with multimodality management. MATERIALS AND METHODS: We conducted a retrospective analysis between 2010 to 2020 of all mediastinal germ cell tumors registered at our center. Data on patient demographics, treatments received, treatment toxicities and response were recorded. Overall survival and relapse free survival were estimated using Kaplan-Meier methods. RESULTS: A total of 30 patients were identified. The median age was 25.5 (range, 18-45) years. Common presenting features included cough (70%) and shortness of breath (70%). Histology wise, 60% patients were non seminomatous histology, whereas 33.3% patients were Seminoma. Twenty-seven (90%) patients received chemotherapy as the first-line treatment, of whom five patients (16.6%) underwent surgery and radiation therapy subsequently. Median follow-up was 26.9 months. Thirteen patients (43.3%) had complete response (43.3%) and eight patients had partial response (26.7%), while three patients (5.5%) had progressive disease. Three-year relapse-free survival rate was 69.6% (95% confidence interval [CI], 42.8-85.6%). Overall survival (OS) at 3 years was 73.4% (95% CI, 49.4-87.3%). Patients with seminoma had a 3 year OS of 90.0% (95% CI, 47.3-98.5%) compared to those with non-seminoma (63.53% [95% CI, 32.3-83.3%]). CONCLUSIONS: Multiagent chemotherapy is the backbone of treatment in PMGCT. Seminomatous PMGCT have excellent prognosis, while further improvement is needed in those with nonseminomatous tumor.

Fertility and pregnancy in chronic myeloid leukemia: real-world experience from an Indian tertiary care institution.

Chronic myeloid leukemia (CML) management during pregnancy is challenging. In this retrospective study, hospital records of CML patients treated between 2000 and 2021 were screened to identify patients who tried to conceive/got pregnant (planned and unplanned) on TKIs (tyrosine kinase inhibitors)/were pregnant at CML onset/fathered a child. We found ninety-three pregnancies involving thirty-three women and thirty-eight men, and they were analyzed for the pregnancy outcomes and the strategies utilized for CML management during pregnancy and the pre-conception period. There were two women and four men with primary infertility and five women with secondary infertility. TKIs were discontinued before conception in four planned pregnancies and at the time of recognition of pregnancy in unplanned pregnancies (n = 21). Unplanned pregnancy outcomes were two miscarriages, eight elective terminations, and eleven live births. Planned pregnancies led to four healthy babies. Outcomes of pregnancies at CML onset (n = 17) were six live births, one stillbirth, five elective terminations, and five abortions. Except for one child with congenital micro-ophthalmia, no other child born to the women on TKI had any malformations. Thirty-eight men fathered 51 healthy children. All but two patients (one planned and one unplanned pregnancy) lost their hematological responses during pregnancy and gained their previous best response after restarting TKI. In women who were pregnant at CML onset, complete cytological remission (CCYR) was achieved between 7 and 24 months (median:14 months) after starting TKI. During pregnancy, intermittent hydroxyurea ± TKI (in the second and third trimesters) was used to keep WBCs less than 30,000/mm3. Outcomes of pregnancies in CML patients can be optimized with our approach. TKIs (Imatinib and Nilotinib) can be safely used in the second and third trimesters. Delayed initiation or interruption of TKI during pregnancy does not negatively affect response to TKIs.

Temperature dependent characteristics of flexible p-PANI/n-ZnO based hybrid heterojunction diode.

This study aims to develop and characterize a flexible p-PANI/n-ZnO heterojunction diode developed from a combination of electrochemical and sputtering technique. Investigation of structural properties and morphology of the thin films has been done from XRD and SEM analysis. To study the temperature effect on the electrical properties of the diode, current-voltage-temperature (I-V-T) measurements were done for the temperature range 25-300 K. Applying the ideal thermionic emission theory, various diode parameters like reverse saturation current, quality factor, series resistance and barrier height were computed utilizing the semilogarithmic plot ofI-Vcurve and Cheungs' method. Barrier height, reverse saturation current and quality factor calculated from ln(I)versusVcurve were observed to vary from 0.0627-0.725 eV, 0.236-98.8 nA and 54.43-3.29 respectively over the temperature range 25-300 K. It has been found that the series resistance falls with a rise in temperature. The barrier height, series resistance and ideality factor were observed to vary from 0.0628-0.692 eV, 15 900-46.8 Kohm and 41.88-2.27 respectively for the temperature range 25-300 K. The activation energy estimated from Arrhenius plot was observed to be 14.51 meV. Additionally, the fabricated PANI/ZnO diode was mechanically robust that can be bent without affecting its performance.

Role of organisms and their enzymes in the biodegradation of microplastics and nanoplastics: A review.

Microplastic (MP) and Nanoplastic (NP) contamination have become a critical ecological concern due to their persistent presence in every aspect of the ecosystem and their potentially harmful effects. The current approaches to eradicate these wastes by burning up and dumping adversely impact the environment, while recycling has its own challenges. As a result, applying degradation techniques to eliminate these recalcitrant polymers has been a focus of scientific investigation in the recent past. Biological, photocatalytic, electrocatalytic, and, recently, nanotechnologies have been studied to degrade these polymers. Nevertheless, it is hard to degrade MPs and NPs in the environment, and these degradation techniques are comparatively inefficient and require further development. The recent research focuses on the potential use of microbes to degrade MPs and NPs as a sustainable solution. Therefore, considering the recent advancements in this important research field, this review highlights the utilization of organisms and enzymes for the biodegradation of the MPs and NPs with their probable degradation mechanisms. This review provides insight into various microbial entities and their enzymes for the biodegradation of MPs. In addition, owing to the lack of research on the biodegradation of NPs, the perspective of applying these processes to NPs degradation has also been looked at. Finally, a critical evaluation of the recent development and perspective for future research to improve the effective removal of MPs and NPs in the environment through biodegradation is also discussed.

Combinatorial approaches of nanotherapeutics for inflammatory pathway targeted therapy of prostate cancer.

Prostate cancer (PC) is the most prevalent male urogenital cancer worldwide. PC patients presenting an advanced or metastatic cancer succumb to the disease, even after therapeutic interventions including radiotherapy, surgery, androgen deprivation therapy (ADT), and chemotherapy. One of the hallmarks of PC is evading immune surveillance and chronic inflammation, which is a major challenge towards designing effective therapeutic formulations against PC. Chronic inflammation in PC is often characterized by tumor microenvironment alterations, epithelial-mesenchymal transition and extracellular matrix modifications. The inflammatory events are modulated by reactive nitrogen and oxygen species, inflammatory cytokines and chemokines. Major signaling pathways in PC includes androgen receptor, PI3K and NF-κB pathways and targeting these inter-linked pathways poses a major therapeutic challenge. Notably, many conventional treatments are clinically unsuccessful, due to lack of targetability and poor bioavailability of the therapeutics, untoward toxicity and multidrug resistance. The past decade witnessed an advancement of nanotechnology as an excellent therapeutic paradigm for PC therapy. Modern nanovectorization strategies such as stimuli-responsive and active PC targeting carriers offer controlled release patterns and superior anti-cancer effects. The current review initially describes the classification, inflammatory triggers and major inflammatory pathways of PC, various PC treatment strategies and their limitations. Subsequently, recent advancement in combinatorial nanotherapeutic approaches, which target PC inflammatory pathways, and the mechanism of action are discussed. Besides, the current clinical status and prospects of PC homing nanovectorization, and major challenges to be addressed towards the advancement PC therapy are also addressed.

Intuitive evaluation of contemporary management strategies in thymoma - the largest Indian experience.

Background: The aim was perusal of the treatment strategies, clinical outcomes and factors impacting these outcomes in thymoma. Materials and methods: A total of 119 patients diagnosed and treated cases of thymoma, at our hospital, were taken for analysis. Thirty-one patients were excluded due to inadequate medical records. Descriptive statistics were used to report demographic and clinical characteristics. Time period between diagnosis and death was defined as overall survival (OS). Multivariate analysis (MVA), using cox regression modelling, was done by including clinicopathological factors in a bid to identify prognostic factors influencing OS. SPSS version 26 was used for statistical analysis. Results: The mean age of the patients was 52.17 years and 39 (44.3%), 19 (21.6%), 17 (1.3%) and 13 (4.8%) patients presented with Masaoka stage II, IV, III and I, respectively. Surgery was done in 64 (72.7%) of the patients as a part of the treatment strategy. Radiotherapy was administered to a total of 57 patients with a median dose of 50.4 Gy. Early Masaoka stage at presentation and use of surgery in the treatment plan were statistically significant prognostic factors for a better overall survival on multivariate analysis. Conclusion: Judicious use of radiotherapy and chemotherapy in locally advanced cases may render them resectable. In a bid to gain good survival rates, aggressive multimodality treatment should be offered to the patients.

Bendamustine in combination with pomalidomide and dexamethasone in relapsed/refractory multiple myeloma: A phase II trial.

Treatment of patients with resistant/refractory multiple myeloma (MM) is an unmet need. In this phase II study, we evaluated the role of bendamustine, pomalidomide and dexamethasone combination in this setting. Between February 2020 and December 2021, 28 patients were recruited. Patients received bendamustine 120 mg/m2 day 1, pomalidomide 3 mg days 1-21, and dexamethasone 40 mg days 1, 8, 11, 22, regimen given for a maximum of six cycles. The median (range) age of the patients was 54 (30-76) years and 15 (53.6%) were males. Patients had received a median (range) of three (two-six) prior lines and 85.7% were refractory to both lenalidomide and bortezomib. The primary end-point was the overall response rate (ORR) defined as ≥partial response after at least three cycles. Secondary objectives were toxicity, progression-free survival (PFS), time to progression and overall survival (OS). An intent-to-treat analysis was done. An ORR of 57.6% was achieved. Patients with extramedullary myeloma had a better response rate. At a median follow-up of 8.6 months, the median PFS and OS were 6.2 and 9.7 months respectively. Toxicity was manageable; mainly haematological (neutropenia, 46.4%; anaemia, 42.8%; and thrombocytopenia, 7.1%). Bendamustine, pomalidomide and dexamethasone could be a novel combination for the heavily pretreated, lenalidomide-refractory myeloma population.

Effect of fetal liver condition media derived cytokines(IL-6 and Flt-3) on human bone marrow stem cells colony formation.

Earlier research from our laboratory demonstrated the presence of stimulatory activity of different growth factors in the fetal liver (FL) extracts when collected in a medium known as fetal liver conditioned medium (FLCM) using Enzyme-linked Immunosorbent Assay (ELISA). In the present study, we have assessed two other cytokines viz. IL-6 and FMS like tyrosine kinase-3 (Flt-3) with the help of bioneutralization assay. FLCM was prepared by incubating fetal liver cells with Iscove's Modified Dulbecco's Medium (IMDM) containing 10% fetal bovine serum (FBS) and 10% Phytohemagglutinin and collected after 24hrs, 48hrs, 72 hrs. and on the 7th day of incubation. Clonal cultures were established for 1 X 105 normal bone marrow (BM) mononuclear cells (NBM MNC) per plate with methylcellulose medium containing cytokines SCF and EPO. Mean Colony forming units-granulocytes, erythrocytes, macrophages, megakaryocytes (CFU-GEMM) were assessed with and without the addition of FLCM. It was found that FLCM enhanced the number of colonies made by NBM MNCs. Further, cytokines IL-6 and Flt-3, present in FLCM, were bioneutralized with respective anti-cytokine antibodies. Neutralized FLCM was evaluated for the colony-forming potential of CFU-GEMM colonies. The maximum reduction of 42% was seen with 20 ng/ml of anti-IL-6 antibody. Maximum suppression up to 20% was observed with 0.7 ng/ml of anti Flt-3 antibody for CFU-GEMM colonies. Presence of cytokines IL-6 and Flt-3 in FL extracts and their colony stimulatory activity suggests that fetal liver infusion (FLI) may be a valuable alternative for managing BM recovery in certain clinical conditions such as AA.

Quercetin Impairs HuR-Driven Progression and Migration of Triple Negative Breast Cancer (TNBC) Cells.

In the present study, we have explored the prognostic value of HuR gene as well as protein in breast cancers. Furthermore, we have also investigated the HuR therapeutic relevance in TNBCs, which is an aggressive breast cancer subtype. Using an online meta-analysis tool, we found that HuR protein overexpression positively correlates with reduced overall survival of TNBC patients (p = 0.028). Furthermore, we demonstrated that the TNBC breast cancer cell lines i.e., MDA-MB-231 and MDA-MB-468 are good model systems to study HuR protein, as they both exhibit a significant amount of cytoplasmic HuR (active form). Quercetin treatment significantly inhibited the cytoplasmic HuR in both TNBC cell lines. By using specific HuR siRNA, we established that quercetin-mediated inhibition of adhesion and migration of TNBC cells is dependent on HuR. Upon analyzing adhesion proteins i.e., ß-catenin and CD44, we found that quercetin mediated effect on TNBC adhesion and migration was through the HuR-ß-catenin axis and CD44, independently. Overall, the present results demonstrate that elevated HuR levels are associated with TNBC progression and relapse, and the ability of quercetin to inhibit cytoplasmic HuR protein provides a rationale for using it as an anticancer agent for the treatment of aggressive TNBCs.Supplemental data for this article is available online at at 10.1080/01635581.2021.1952628.

Characteristics & outcomes of cancer patients with COVID-19: A multicentre retrospective study from India.

Background & objectives: High mortality has been observed in the cancer population affected with COVID-19 during this pandemic. We undertook this study to determine the characteristics and outcomes of cancer patients with COVID-19 and assessed the factors predicting outcome. Methods: Patients of all age groups with a proven history of malignancy and a recent diagnosis of SARS-CoV-2 infection based on nasal/nasopharyngeal reverse transcriptase (RT)-PCR tests were included. Demographic, clinical and laboratory variables were compared between survivors and non-survivors groups, with respect to observed mortality. Results: Between May 11 and August 10, 2020, 134 patients were included from the three centres and observed mortality was 17.1 per cent. The median age was 53 yr (interquartile range 39-61 yr) and thirty four patients (25%) were asymptomatic. Solid tumours accounted for 69.1 per cent and breast cancer was the most common tumour type (20%). One hundred and five patients (70.5%) had received chemotherapy within the past four weeks and 25 patients (19.3%) had neutropenia at presentation. On multivariate analysis, age [odds ratio (OR) 7.99 (95% confidence interval [CI] 1.18-54.00); P=0.033], haemoglobin [OR 6.28 (95% CI 1.07-37.04); P=0.042] neutrophil-lymphocyte ratio [OR 12.02 (95% CI 2.08-69.51); P=0.005] and baseline serum albumin [OR 18.52 (95% CI 2.80-122.27); P=0.002], were associated with higher mortality. Recent chemotherapy, haematological tumours type and baseline neutropenia did not affect the outcome. Interpretation & conclusions: Higher mortality in moderate and severe infections was associated with baseline organ dysfunction and elderly age. Significant proportion of patients were asymptomatic and might remain undetected.

Evaluation of serum glucose-regulated protein 78 (GRP78) as a biomarker of treatment response to bortezomib-based induction regimen in multiple myeloma: A cross-sectional pilot study.

GRP78 overexpression in myeloma cells has been associated with bortezomib resistance in multiple myeloma (MM). However, serum GRP78 as a maker of bortezomib-based treatment response remains unexplored. The objective of the study was to evaluate serum GRP78 levels in MM patients who underwent a bortezomib-based induction regimen. This cross-sectional study included adult MM patients (n=30) who completed at least four cycles of bortezomib-based induction therapy. Healthy volunteers (n=30) and newly diagnosed MM patients (n=19) were also recruited to identify the disease-associated change in GRP78 levels. Serum GRP78 was estimated by ELISA. Surface and intracellular expression of GRP78 in bone marrow plasma cells was evaluated in ten MM patients by flow cytometry. Among 30 MM patients [median (range): 52 (38-68) years; 20 males] who completed at least four cycles of bortezomib-based induction therapy, 20 were responders and 10 were non-responders. Serum GRP78 levels were not significantly different between responders [median (IQR): 5.2 (3.1, 8.0) µg/ml] and non-responders [median (IQR): 4.3 (0.1, 7.1) µg/ml] (p=0.4). Although non-significant (p=0.3), median serum GRP78 was higher in newly diagnosed patients when compared to healthy volunteers. Bone marrow plasma cells ranged from 0.2 to 57.8% in the analyzed samples. Intracellular GRP78 expression in bone marrow plasma cells was higher (1.6 to 5 times) when compared to surface expression. To conclude, serum GRP78 levels vary widely in different MM patient groups but did not correlate with response to a bortezomib-based induction regimen.

Molecular characterization of Clostridioides difficile by multi-locus sequence typing (MLST): A study from tertiary care center in India.

OBJECTIVES: Clostridioides difficile is an important pathogen responsible for antibiotic-associated diarrhoea (AAD). This study was aimed to perform multi-locus sequence typing (MLST) of C. difficile isolates from AAD cases and to understand the clonal relationship between these C. difficile strains. METHODS: Thirty five strains and a standard strain C.difficile ATCC 9689 were characterized by polymerase chain reaction assay (PCR) for toxin genes (tcdA and tcdB gene) detection and MLST. RESULTS: MLST results revealed that the most common sequence types were ST-17, ST-54, ST-63. The cluster analysis revealed that strains isolated from AAD patients generated 12 MLST sequence types grouped into two distinct evolutionary lineages. CONCLUSIONS: ST 17 is most prominent sequence type. This is the first report of MLST based study of C. difficile from India. Further studies from diverse geographical regions can help better understand the epidemiology of CDI in India.

Advancements in laundry wastewater treatment for reuse: a review.

Laundry related activities produce huge quantity of wastewater that is very rich in lint, dyes, surfactants, and detergents. The large amount of laundry wastewater (LWW) is generated by extensive human activities. LWW needs to be treated in order to tackle the challenging problem of water pollution and to accomplish water sustainability. To achieve this success, LWW can be reused for several purposes such as irrigation, construction activities, vehicle washing etc. However, there are several challenges in the reclamation of LWW like effective handling of the wastewater and meeting the regulatory criteria. Based on the literature review it seems that a single treatment process is not sufficient to treat LWW up to acceptable reuse standards. To that end, different treatment chains have been proposed: i) hybrid processes combining membrane filtration with adsorption; ii) advanced oxidation process using ultraviolet (UV) and hydrogen peroxide (H2O2); iii) coagulation-flocculation combined with sand filtration; iv) combination of ozonation process, adsorption, and ultrafiltration (UF). This review paper discusses the selection of suitable treatment technology depends on several factors: i) a well-designed equipment, ii) cost-effectiveness of treatment method and iii) desired characteristics of the treated water. The review paper also presents solutions for treatment and reclamation of LWW.

Anti-oxidant Containing Nanostructured Lipid Carriers of Ritonavir: Development, Optimization, and In Vitro and In Vivo Evaluations.

Acquired immunodeficiency syndrome (AIDS) is a condition caused by the infection of a retrovirus namely, human immunodeficiency virus (HIV). Currently, highly active anti-retroviral therapy (HAART), a combination of anti-viral drugs belonging to different classes is considered to be effective in the management of HIV. Ritonavir, a protease inhibitor (PI), is one of the most important components of the HAART regimen. Because of its lower bioavailability and severe side effects, presently, ritonavir is not being used as a PI. However, this drug is being used as a pharmacokinetic boosting agent for other PIs such as lopinavir and in lower doses. The current study aimed to develop nanostructured lipid carriers (NLCs) encapsulating ritonavir to reduce its side effects and enhance oral bioavailability. Ritonavir-loaded NLCs were developed using a combination of two different solid lipids and liquid lipids. Alpha-tocopherol, a well-known anti-oxidant, was used as an excipient (liquid lipid) in the development of NLCs which were prepared using a simple hot-emulsion and ultrasonication method. Drug-excipient studies were performed using Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). QbD approach was followed for the screening and optimization of different variables. The developed NLCs were characterized for their particle size (PS), polydispersity index (PDI), zeta potential (ZP), and entrapment efficiency (EE). Furthermore, NLCs were studied for their in vitro drug release profile, and finally, pharmacokinetic parameters were determined using in vivo pharmacokinetic studies. The optimized NLC size was in the range of 273.9 to 458.7 nm, PDI of 0.314 to 0.480, ZP of -52.2 to - 40.9 mV, and EE in the range of 47.37 to 74.51%. From in vitro drug release, it was found that the release of drug in acidic medium was higher than phosphate buffer pH 6.8. Finally, in vivo pharmacokinetic studies revealed a 7-fold enhancement in the area under the curve (AUC) and more than 10-fold higher Cmax with the optimized formulation in comparison to pure drug suspension. Graphical Abstract.

3D Printing: Applications in Tissue Engineering, Medical Devices, and Drug Delivery.

The gemstone of 3-dimensional (3D) printing shines up from the pyramid of additive manufacturing. Three-dimensional bioprinting technology has been predicted to be a game-changing breakthrough in the pharmaceutical industry since the last decade. It is fast evolving and finds its seats in a variety of domains, including aviation, defense, automobiles, replacement components, architecture, movies, musical instruments, forensic, dentistry, audiology, prosthetics, surgery, food, and fashion industry. In recent years, this miraculous manufacturing technology has become increasingly relevant for pharmaceutical purposes. Computer-aided drug (CAD) model will be developed by computer software and fed into bioprinters. Based on material inputs, the printers will recognize and produce the model scaffold. Techniques including stereolithography, selective laser sintering, selective laser melting, material extrusion, material jetting, inkjet-based, fused deposition modelling, binder deposition, and bioprinting expedite the printing process. Distinct advantages are rapid prototyping, flexible design, print on demand, light and strong parts, fast and cost-effective, and environment friendly. The present review gives a brief description of the conceptional 3-dimensional printing, followed by various techniques involved. A short note was explained about the fabricating materials in the pharmaceutical sector. The beam of light is thrown on the various applications in the pharma and medical arena.

Transdermal Delivery of Curcumin-Loaded Solid Lipid Nanoparticles as Microneedle Patch: an In Vitro and In Vivo Study.

Curcumin is well known for its neuroprotective effect, and also able to alleviate Parkinsonian features. Clinical application of curcumin is limited due to its low bioavailability. Hence, we hypothesized that the microneedles (MN) containing drug-loaded solid lipid nanoparticles (SLNs) may be able to improve its bioavailability and efficacy. The SLNs were prepared with microemulsion technique using glyceryl monostearate as a lipid and tween 80 as a stabilizer. The particle size, polydispersity index, zeta potential, and entrapment efficiency of prepared SLNs were determined. The optimized formulation was incorporated into microneedle arrays using micromolding technique and fabricated microneedle patch were characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, optical microscopy, ex vivo permeation studies, histology studies, and fluorescent microscopy. The fabricated microneedle patch was also evaluated for neuroprotective activity and skin irritation potential. Fourier transform infrared spectroscopy studies of SLNs and microneedles confirmed the chemical compatibility of excipients with curcumin. The developed microneedles were also found to be non-irritant with decreased degree of bradykinesia, high motor coordination, and balance ability. The study provided a theoretical basis for the use of novel microneedle containing curcumin-loaded solid lipid nanoparticles as a useful tool for the treatment of Parkinson's disease.

Impact of climate change on Asiatic black bear (Ursus thibetanus) and its autumn diet in the northern highlands of Pakistan.

Approximately 20%-30% of plant and animal species are at risk of extinction by the end of the 21st century owing to climate change. Range shifts and range contractions in plant species will dramatically affect the distribution of animals relying on them for food and shelter. The negative impacts of climate change on forested landscapes of the northern highlands of Pakistan (NHP) could change the species composition and distribution. The Asiatic black bear (Ursus thibetanus), a forest-dwelling species, primarily depends on plants for foraging, and is assumed to be affected by climate change in NHP. Scat analyses and indigenous knowledge from Machiara National Park revealed the maximum consumption of Quercus species (natural food) and Zea mays (human grown food) by the Asiatic black bear in autumn season. We collected the occurrence data of the Asiatic black bear and its commonly used food (three Quercus spp.) in the NHP. We used the MaxEnt model to simulate current and future (in 2050 and 2070) distribution of the species under RCP4.5 (medium carbon emission scenario) and RCP8.5 (extreme carbon emission scenario). The results predict range reduction and extreme fragmentation in the habitats of all the Quercus spp. Besides, a dramatic decrease in the suitable (SH) and very highly suitable (HSH) habitats was predicted in the future. Range shift and range reduction of Quercus spp. may interrupt the denning chronology of Asiatic black bears, escalate the human-black bear conflicts and local extirpation of the species. Given the extent and magnitude of climate change, it will likely not be enough to focus solely on the conservation of the Asiatic black bear. We need more dynamic planning aiming at mitigating the effect of climate change in forested landscapes including the Quercus forests.