Autologous hematopoietic stem cell transplantation conditioning regimens and chimeric antigen receptor T cell therapy in various diseases.

Conditioning regimens employed in autologous stem cell transplantation have been proven useful in various hematological disorders and underlying malig nancies; however, despite being efficacious in various instances, negative consequences have also been recorded. Multiple conditioning regimens were extracted from various literature searches from databases like PubMed, Google scholar, EMBASE, and Cochrane. Conditioning regimens for each disease were compared by using various end points such as overall survival (OS), progression free survival (PFS), and leukemia free survival (LFS). Variables were presented on graphs and analyzed to conclude a more efficacious conditioning regimen. In multiple myeloma, the most effective regimen was high dose melphalan (MEL) given at a dose of 200/mg/m2. The comparative results of acute myeloid leukemia were presented and the regimens that proved to be at an admirable position were busulfan (BU) + MEL regarding OS and BU + VP16 regarding LFS. In case of acute lymphoblastic leukemia (ALL), BU, fludarabine, and etoposide (BuFluVP) conferred good disease control not only with a paramount improvement in survival rate but also low risk of recurrence. However, for ALL, chimeric antigen receptor (CAR) T cell therapy was preferred in the context of better OS and LFS. With respect to Hodgkin's lymphoma, mitoxantrone (MITO)/MEL overtook carmustine, VP16, cytarabine, and MEL in view of PFS and vice versa regarding OS. Non-Hodgkin's lymphoma patients were administered MITO (60 mg/m2) and MEL (180 mg/m2) which showed promising results. Lastly, amyloidosis was considered, and the regimen that proved to be competent was MEL 200 (200 mg/m2). This review article demonstrates a comparison between various conditioning regimens employed in different diseases.

Environmental implication and cancer risk assessment of residual pollutants in cotton crop: a case study of Multan District, Pakistan.

Pakistan is the fourth largest yarn producer in the world heavily that relies on cotton crop which receives a substantial 62% of all pesticide applications. The present study was conducted to quantify the levels of pesticides such as bifenthrin, spirotetramat, pyriproxyfen, imidacloprid, and diafenthiuron in soil and plants residue at selected cotton fields of Multan District, Pakistan. In addition to pesticides, the assessment of heavy metal concentration was also conducted in order to determine the overall risks that these compounds to both plants and human population. For this analysis, 20 soil samples and 10 plant samples were collected from 10 selected cotton fields. Pesticides and heavy metals in soil and plant samples were analyzed using high-performance liquid chromatography (HPLC) and Inductively Coupled Plasma-Optical Emission Spectroscopy (ICP-OES), respectively. It was observed that all samples collected from selected fields contained pesticide residue in top soil (0-15 cm). However, no pesticides were detected in the lower soil layer (16-30 cm). In case of heavy metals, the highest concentration of Fe, Pb, and Mn was observed in both soil and plant residue samples. The heavy metals were found in the order of Fe > Mn > Pb > Zn > Cu > Cd in the soil. The total carcinogenic risk values for a few pesticides were found to range from 10-6 to 10-2, indicating that residents of the study area have low to higher chances of developing cancer. A positive correlation was observed among the pesticides (r = 0.18-0.95) as well as in metals related parameters (r = 0.49-0.96), where a weak negative correlation was found among metal to pesticide parameters except Pd where the maximum r value was 0.62. In general, the finding of this study encourages the development and adoption of sustainable agricultural practices that lower the dependence on toxic pesticides and endorse environmentally friendly alternatives.

Waldenström macroglobulinemia: a review of pathogenesis, current treatment, and future prospects.

Waldenström macroglobulinemia (WM) is a chronic B-cell lymphoproliferative disorder characterized by lymphoplasmacytic cell overgrowth in the bone marrow and increased secretion of IgM immunoglobulins into the serum. Patients with WM have a variety of clinical outcomes, including long-term survival but inevitable recurrence. Recent advances in disease knowledge, including molecular and genetic principles with the discovery of MYD88 and CXCR4 mutations, have rapidly increased patient-tolerable treatment options. WM patients may benefit from chemotherapy regimens that include rituximab-based regimens, alkylating drugs, proteasome inhibitors, monoclonal antibodies, and drugs targeting Bruton tyrosine kinase inhibitors. In light of these advancements, patients can now receive treatment customized to their specific clinical characteristics, focusing on enhancing the depth and durability of their response while limiting the adverse effects. Despite the rapidly developing therapeutic armament against WM, a lack of high-quality evidence from extensive phase 3 trials remains a significant challenge in the research. We believe clinical outcomes will keep improving when new medicines are introduced while preserving efficacy and minimizing toxicity.

Association Between Levels of Pre-operative Glycosylated Hemoglobin and Post-operative Surgical Site Infections After Elective Surgery in a Low-Income Country.

INTRODUCTION: Diabetic patients undergoing surgery are more susceptible to hospital-acquired infection, particularly surgical site infection (SSI). Good glycemic control in preoperative patients significantly decreases the risk of SSI. There is a scarcity of data from low-income countries studying the relation between perioperative glycated hemoglobin (HbA1c) levels and postoperative SSI. We aim to establish statistical relation between HbA1c and SSI which will help decrease post-operative infections and morbidity. METHODS: This study was conducted in the surgical unit of Jinnah Sindh Medical University, Karachi, Pakistan, from August 2020 to April 2022. Patients who underwent elective surgical procedures (n= 1024) were included in the study and divided into two groups based on their HbA1c levels. Patients with HbA1c levels higher than 6.5% were classified as group A and those with HbA1c less than 6.5% belonged to group B. For statistical analysis, IBM SPSS Statistics for Windows, Version 24.0 (Released 2016; IBM Corp., Armonk, New York, United States) was used. RESULTS: Group A comprised 579 (56.5%) patients. The presence of SSI in participants with HbA1c >6.5% was statistically significant (p-value: 0.011). Genderwise comparison with the presence of SSI was found to be insignificant (p-value: 0.28). Smoking was positively correlated with the absence of SSI. No significance in terms of presence or absence of SSI was found in the comparison of the type of wounds (p-value: 0.25). CONCLUSION:  There is a positive relationship between raised HbA1c levels and the development of SSI. Our study emphasizes the importance of the use of HbA1c levels as a more accurate predictor of glycemic control in pre-operative patients rather than blood glucose levels. It is imperative that surgeons must check HbA1c levels before selecting patients for elective surgeries, especially in low-income countries where the healthcare burden is already huge.

Phycoremediation of textile effluents with enhanced efficacy of biodiesel production by algae and potential use of remediated effluent for improving growth of wheat.

The uncontrolled industrialization and unrestricted textile production combined with inappropriate effluent treatment services in developing countries like Pakistan have multiplied the number of harmful effluent discharge. These effluents are enriched with dyes, heavy metal ions, and other hazardous materials that are poisonous and carcinogenic to living organisms. For that reason, the utilization of economic and efficient control techniques against such pollutants is imperative to protect natural resources. The triple algal role for phycoremediation of textile effluent was utilized in this study to make it suitable for irrigation and higher biofuel production. Locally isolated two strains, CKW1 (Spirogyra sp.) and PKS33 (Cladophora sp.), were used to treat the effluent collected from the direct outlets of the textile industries. The treated effluent was then tested for its toxicity and applied to wheat at initial stage grown under axenic conditions to check its effect on wheat (Triticum aestivum L.) vegetative growth and development. Finally, the algal biomass obtained after treatment was subjected to trans-esterification for predicting the amount of biodiesel production. Study outcomes revealed that the algal strains were able to decolorize the effluent entirely within 96-120 h. Compared to un-treated textile effluent, the phycoremediated wastewater application to wheat plants enhanced the plant biomass by 80%. Lastly, the production of biodiesel from algal biomass attained after phycoremediation was 35% less to algal biomass obtained under normal growth conditions. It can be concluded that the algal use helps to treat the contaminated effluent and marks them re-usable for irrigating plants and producing biomass which could be utilized for biodiesel production.

Environmental variables influence the developmental stages of the citrus leafminer, infestation level and mined leaves physiological response of Kinnow mandarin.

Climate change has not only exacerbated abiotic stress, but has also rendered external conditions more feasible for pests to spread and infest citrus fruit. Citrus leafminer (Phyllocnistis citrella) is a potential pest that directly feeds the newly sprouted leaves and twigs of all three spring, summer and autumn flushes. Increasing temperatures in spring and autumn, leafminer accrued more heat units or developmental degree days to accelerate the biological stages of its life-cycle, thereby increasing the pressure of infestation. Present work was conducted at three different environmental conditions in Sargodha, Toba Tek Singh (TTS) and Vehari districts of the Punjab province, Pakistan; all three experimental sites were located in different agro-ecological zones. More infestation was recorded in all three flushes at TTS and Vehari than in Sargodha. Overall, more damage was observed due to higher temperatures in TTS and Vehari than in Sargodha. After May-June heat stress, spontaneous vegetative growth continued from July to November, produced newly spouted tender leaves for feeding the leafminer larvae, and was seen more in TTS and Vehari. Leafminer larva prefers to enter young and tender leaves with a maximum entrance in leaves up to 1 cm2 in size while observing no entrance above 3 cm2 of leaf size. Physiological response of leaves primarily attributed to chlorophyll and carotenoid contents, both of which were recorded lower in the mined leaves, thereby reducing leaf photosynthetic activity. Similarly, lower levels of polyphenols and antioxidant activity were also recorded in the mined leaves. The on-tree age of mined leaves of three vegetative flushes of Kinnow plant was also less counted than non-mined leaves. Climate change has affected vegetative phenology and become feasible for pests due to extemporaneous leaf growth, particularly leafminer, and eventually causes economic loss by supplying low carbohydrates either to hanging fruits or next-season crops.

Effects of plant growth-promoting rhizobacteria strains producing ACC deaminase on photosynthesis, isoprene emission, ethylene formation and growth of Mucuna pruriens (L.) DC. in response to water deficit.

Agricultural sustainability is an increasing need considering the challenges posed by climate change and rapid human population growth. The use of plant growth-promoting rhizobacteria (PGPR) may represent an excellent, new agriculture practice to improve soil quality while promoting growth and yield of important crop species subjected to water stress conditions. In this study, two PGPR strains with 1-Aminocyclopropane-1-Carboxylate (ACC) deaminase activity were co-inoculated in velvet bean plants to verify the physiological, biochemical and molecular responses to progressive water stress. The results of our study show that the total biomass and the water use efficiency of inoculated plants were higher than uninoculated plants at the end of the water stress period. These positive effects may be derived from a lower root ACC content (-45 %) in water-stressed inoculated plants than in uninoculated ones resulting in lower root ethylene emission. Furthermore, the ability of inoculated plants to maintain higher levels of both isoprene emission, a priming compound that may help to protect leaves from oxidative damage, and carbon assimilation during water stress progression may indicate the underlining metabolic processes conferring water stress tolerance. Overall, the experimental results show that co-inoculation with ACC deaminase PGPR positively affects tolerance to water deficit, confirming the potential for biotechnological applications in water-stressed agricultural areas.

Environmental chromium from the tannery industry induces altered reproductive endpoints in the wild female small Indian mongoose ( Urva auropunctatus).

The populations of wild animals are declining in many parts of the world in response to man-made alterations in the environment. Environmental contamination due to heavy metals discharge from industry may contribute to the decline of wild animal populations by impacting their reproduction, growth, and development. In the leather tanning industry, chromium (Cr) is used as a basic component, but it is a potent toxicant that can affect many of the physiological functions of animals. In the current study, we investigated the reproductive toxicity of industrial Cr in female small Indian mongooses inhabiting a tannery area. Adult female specimens were live trapped from February 2015 to January 2016. Blood and other body tissues (ovaries, kidneys and liver) of the captured specimens were collected along with soil and water samples from the environment for analysis. The Cr concentrations were found significantly ( p < 0.0001) increased compared to control in the environment, blood, and all body tissues of the animals. Estradiol and progesterone levels were found to be significantly decreased in comparison with control ( p < 0.0001), along with reduced ovarian weights, while follicle stimulating hormone (FSH) and luteinizing hormone levels were found significantly ( p < 0.0001) elevated. Light microscopy revealed significantly decreased in comparison with control ovarian follicle numbers ( p < 0.0001) and diameters, vacuolization of the oocytes, and a significantly higher percentage of atretic follicles inside the ovary. We conclude that Cr discharged from the tanneries is absorbed by the exposed female small Indian mongoose, leading to ovarian dysfunction with potential impairment of reproductive function.

Effect of land use activities on PAH contamination in urban soils of Rawalpindi and Islamabad, Pakistan.

Urbanization can increase the vulnerability of soils to various types of contamination. Increased contamination of urban soils with polycyclic aromatic hydrocarbon (PAH) could relate to increased number of petrol pump stations and mechanical workshops-a phenomenon that needs to be constantly monitored. This study was undertaken to explore the soil PAH levels in Rawalpindi and Islamabad urban areas in relation to land use activities. Composite soil samples from petrol pump stations and mechanical workshops (n = 32) areas were evaluated for five PAHs--naphthalene, phenanthrene, pyrene, benzo[a]pyrene, and indeno(1,2,3-cd)pyrene-and compared with control area locations with minimum petroleum-related activity (n = 16). Surface samples up to 3 cm depth were collected and extraction of analytes was carried out using n-hexane and dichloromethane. Prior to running the samples, standards (100 µg ml(-1)) were run on HPLC to optimize signal to noise ratio using acetonitrile as mobile phase at a flow rate of 1.25 ml/min at 40 °C. Significant differences between petrol pump stations and mechanical workshop areas were observed for individual PAH as well as with control area soil samples. Naphthalene was found to be the most abundant PAH in soil, ranging from 2.47 to 24.36 mg kg(-1). Correlation between the benzo[a]pyrene (BaP) level in soil and the total PAH concentration (r = 0.82, P < 0.0001) revealed that BaP can be used as a potential marker for PAH pollution. A clear segregation between petrogenic and pyrogenic sources of contamination was observed when low molecular weight PAHs detected in soil was plotted against high molecular weight PAHs. The former source comprised lubricants and used engine oil found at mechanical workshops, whereas the latter could be mostly attributed to vehicular emission at petrol pumps. The results indicate that PAH contamination in urban areas of Rawalpindi and Islamabad has direct relevance with land use for petroleum activity. We conclude that in order to reduce the soil PAH exposure in urban environment, petrol pumps and mechanical workshops must be shifted to less densely populated areas because of their role as important point sources for PAH emission.