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Spontaneous remission (SR) in acute lymphoblastic leukemia (ALL) is a poorly understood phenomenon that has been sporadically reported in medical literature for over a century, and the molecular and immunologic mechanisms of remission pose interesting clinical questions. Furthermore, the often-transient nature of these remissions poses a challenge to physicians in formulating an approach to treatment. We report on a rare case of sepsis in a three-year-old female with high-risk ALL who received less than two months of treatment prior to sepsis and subsequent SR.

In the present work, the fruits of four Morus species, namely Morus alba （white mulberry）, Morus nigra （black mulberry）, Morus laevigata （large white fruit）, and Morus laevigata （large black fruit）, were analyzed for proximate composition, essential minerals, and antioxidant potentials. For this purpose, the ripe fruits were collected from the northern regions of Pakistan. The major nutritional components （moisture, ash, lipids, proteins, fibres, carbohydrates, and total sugar） were found to be in the suitable range along with good computed energy. Total dry weight, pH, and titratable acidity （percent citric acid） were （17.60±1.94）-（21.97±2.34） mg/100 g, （3.20±0.07）-（4.78±0.15）, and （0.84±0.40）%-（2.00±0.08）%, respectively. Low riboflavin （vitamin B2） and niacin （vitamin B3） contents were recorded in all the fruits, while ascorbic acid （vitamin C） was in the range from （15.20±1.25） to （17.03±1.71） mg/100 g fresh weight （FW）. The mulberry fruits were rich with regard to the total phenol and alkaloid contents, having values of （880±7.20）-（1650±12.25） mg/100 g FW and （390±3.22）-（660±5.25） mg/100 g FW, respectively. Sufficient quantities of essential macro-（K, Ca, Mg, and Na） and micro-（Fe, Zn, and Ni） elements were found in all the fruits. K was the predominant element with concentration ranging from （1270±9.36） to （1731±11.50） mg/100 g, while Ca, Na, and Mg contents were （440±3.21）-（576±7.37）, （260±3.86）-（280±3.50）, and （240±3.51）-（360±4.20） mg/100 g, respectivly. The decreasing order of micro-minerals was Fe〉Zn〉Ni. The radical scavenging activity of methanolic extract of fruits was concentration-dependent and showed a correlation with total phenolic constituents of the respective fruits. Based on the results obtained, mulberry fruits were found to serve as a potential source of food diet and natural antioxidants.

For children with sickle cell anaemia and high transcranial doppler (TCD) flow velocities, regular blood transfusions can effectively prevent primary stroke, but must be continued indefinitely. The efficacy of hydroxycarbamide (hydroxyurea) in this setting is unknown; we performed the TWiTCH trial to compare hydroxyurea with standard transfusions. TWiTCH was a multicentre, phase 3, randomised, open-label, non-inferiority trial done at 26 paediatric hospitals and health centres in the USA and Canada. We enrolled children with sickle cell anaemia who were aged 4–16 years and had abnormal TCD flow velocities (≥200 cm/s) but no severe vasculopathy. After screening, eligible participants were randomly assigned 1:1 to continue standard transfusions (standard group) or hydroxycarbamide (alternative group). Randomisation was done at a central site, stratified by site with a block size of four, and an adaptive randomisation scheme was used to balance the covariates of baseline age and TCD velocity. The study was open-label, but TCD examinations were read centrally by observers masked to treatment assignment and previous TCD results. Participants assigned to standard treatment continued to receive monthly transfusions to maintain 30% sickle haemoglobin or lower, while those assigned to the alternative treatment started oral hydroxycarbamide at 20 mg/kg per day, which was escalated to each participant's maximum tolerated dose. The treatment period lasted 24 months from randomisation. The primary study endpoint was the 24 month TCD velocity calculated from a general linear mixed model, with the non-inferiority margin set at 15 cm/s. The primary analysis was done in the intention-to-treat population and safety was assessed in all patients who received at least one dose of assigned treatment. This study is registered with ClinicalTrials.gov, number NCT01425307. Between Sept 20, 2011, and April 17, 2013, 159 patients consented and enrolled in TWiTCH. 121 participants passed screening and were then randomly assigned to treatment (61 to transfusions and 60 to hydroxycarbamide). At the first scheduled interim analysis, non-inferiority was shown and the sponsor terminated the study. Final model-based TCD velocities were 143 cm/s (95% CI 140–146) in children who received standard transfusions and 138 cm/s (135–142) in those who received hydroxycarbamide, with a difference of 4·54 (0·10–8·98). Non-inferiority (p=8·82 × 10−16) and post-hoc superiority (p=0·023) were met. Of 29 new neurological events adjudicated centrally by masked reviewers, no strokes were identified, but three transient ischaemic attacks occurred in each group. Magnetic resonance brain imaging and angiography (MRI and MRA) at exit showed no new cerebral infarcts in either treatment group, but worsened vasculopathy in one participant who received standard transfusions. 23 severe adverse events in nine (15%) patients were reported for hydroxycarbamide and ten serious adverse events in six (10%) patients were reported for standard transfusions. The most common serious adverse event in both groups was vaso-occlusive pain (11 events in five [8%] patients with hydroxycarbamide and three events in one [2%] patient for transfusions). For high-risk children with sickle cell anaemia and abnormal TCD velocities who have received at least 1 year of transfusions, and have no MRA-defined severe vasculopathy, hydroxycarbamide treatment can substitute for chronic transfusions to maintain TCD velocities and help to prevent primary stroke. National Heart, Lung, and Blood Institute, National Institutes of Health.

We report physicochemical characteristics of various kinds of liquid milk commercially available in Pakistan in comparison with those of fresh natural milk from animals. Milk samples were collected from local markets at Peshawar, Pakistan, and analyzed for their physical features, including moisture, total solids, specific gravity, conductivity, viscosity and titratable acidity （lactic acid equivalent）, and chemical components and macro-minerals, including total protein, casein, lactose, ash and minerals （Na, K and Mg）. These items were compared with the physicochemical characteristics of the fresh natural milk samples from buffalo, cow and goat. The results were also compared with reported nutritional quality of milk from various countries and World Health Organization （WHO） standards. We found that all the physical features and chemical components of commercially available milk in Pakistan markets meet WHO＇s requirements, except for Na, K, Ca and Mg, which are below the standards.

Hepatic veno-occlusive disease is a serious regimen-related toxicity in patients undergoing hematopoietic stem cell transplantation. We performed a systematic review and meta-analysis of the literature on the effect of anticoagulation in preventing veno-occlusive disease. Several databases and online journals were searched for randomized controlled trials and cohort studies. Twelve studies (2782 patients) were eligible. Anticoagulation prophylaxis was associated with a statistically nonsignificant decrease in risk of veno-occlusive disease (pooled relative risk (RR), 0.90; 95% confidence interval (CI), 0.62-1.29). Results of one of three randomized controlled trials may have been affected by delayed introduction of anticoagulation. A second trial enrolled patients who received conventional chemoradiotherapy for early-stage disease (RR, 0.18; 95% CI, 0.04-0.78). The third trial was a pilot study with a small sample size (RR, 0.74; 95% CI, 0.53-1.04). Significant heterogeneity and methodologic weaknesses preclude drawing a meaningful conclusion from the pooled analysis. Despite some limitations, results of two of three eligible randomized controlled trials suggest that prophylactic anticoagulation may help prevent veno-occlusive disease. However, a large randomized controlled trial is needed for confirmation. Additionally, in future studies, owing to the wide spectrum of severity of veno-occlusive disease, outcomes such as 100-day mortality should strongly be considered.

Early secreted antigenic target protein 6 (esat6) is one of the genes present on region of difference 1 (RD1) of Mycobacterium tuberculosis (M. tb) genome. This RD1 is a characteristic of virulent strains of M. tb and Mycobacterium bovis and this is one of the major differences between the disease causing strains and Bacillus-Calmat Guerin (BCG) vaccine strains. Studies have proved the presence of large number of memory T cells in M. tb infected individuals and these memory cells are reactive towards Esat6 antigen, which highlighted the importance of this gene especially in early infections. In this study, numbers of esat6 gene constructs were made in order to get a suitable construct to be used as good DNA vaccine. First esat6 gene construct was made in pND vector without Kozak sequence upstream the gene, second construct was made in pcDNA3.1 vector with Kozak sequence upstream the gene, third construct was made again in pND vector with Kozak sequence, fourth construct was made with Kozak sequence upstream and GGG downstream the ATG as a second codon of gene first in pcDNA3.1 and later in pND vectors respectively which was designated as construct five. Sixth construct was a fusion and in pcDNA3.1 vector with Kozak upstream the gene and epitope V and poly histidine tail sequence provided by vector down stream the gene through in- frame cloning of esat6 gene with sequences provided by vector by removing stop codon through PCR based primers. Seventh and final construct was prepared in pND14 vector also as a fusion construct and gene was cloned under tissue plasminogen activator sequence in an in-frame through PCR based primers. All these constructs were subjected to 293T human embryonic kidney cell lines to evaluate their level of expression. Although none of the constructs gave detectable level of expression in cultured cells when tested through Western blots (WB) but tpa-esat6-pND14 construct was selected as potential DNA vaccine candidate to inject intramuscularly and interadermally to balb/c mice along with controls to obtain detectable response in vivo. Animals were tested nine weeks post vaccination and found positive against tpa-esat6-pND14 vaccine through WB and multiplex micro bead immunoassay (MMIA).

Background Salinity is a major threat to the agriculture industry due to the negative impact of salinity stress on crop productivity. In the present study, we isolated rhizobacteria and evaluated their capacities to promote crop growth under salt stress conditions. Results We isolated rhizospheric bacteria from sand dune flora of Pohang beach, Korea, and screened them for plant growth-promoting (PGP) traits. Among 55 bacterial isolates, 14 produced indole-3-acetic acid (IAA), 10 produced siderophores, and 12 produced extracellular polymeric and phosphate solubilization. Based on these PGP traits, we selected 11 isolates to assess for salinity tolerance. Among them, ALT29 and ALT43 showed the highest tolerance to salinity stress. Next, we tested the culture filtrate of isolates ALT29 and ALT43 for IAA and organic acids to confirm the presence of these PGP products. To investigate the effects of ALT29 and ALT43 on salt tolerance in soybean, we grew seedlings in 0 mM, 80 mM, 160 mM, and 240 mM NaCl treatments, inoculating half with the bacterial isolates. Inoculation with ALT29 and ALT43 significantly increased shoot length (13%), root length (21%), shoot fresh and dry weight (44 and 35%), root fresh and dry weight (9%), chlorophyll content (16–24%), Chl a (8–43%), Chl b (13–46%), and carotenoid (14–39%) content of soybean grown under salt stress. Inoculation with ALT29 and ALT43 also significantly decreased endogenous ABA levels (0.77-fold) and increased endogenous SA contents (6–16%), increased total protein (10–20%) and glutathione contents, and reduced lipid peroxidation (0.8–5-fold), superoxide anion (21–68%), peroxidase (12.14–17.97%), and polyphenol oxidase (11.76–27.06%) contents in soybean under salinity stress. In addition, soybean treated with ALT29 and ALT43 exhibited higher K + uptake (9.34–67.03%) and reduced Na + content (2–4.5-fold). Genes involved in salt tolerance, GmFLD19 and GmNARK , were upregulated under NaCl stress; however, significant decreases in GmFLD19 (3–12-fold) and GmNARK (1.8–3.7-fold) expression were observed in bacterial inoculated plants. Conclusion In conclusion, bacterial isolates ALT29 and ALT43 can mitigate salinity stress and increase plant growth, providing an eco-friendly approach for addressing saline conditions in agricultural production systems.

Salinity is a significant abiotic stress for crop plants and a threat to global food security. Optimizing yield without adversely affecting the ecosystem is necessary for a sustainable agriculture. Silicon and plant growth-promoting bacteria were reported for mitigating several abiotic and biotic stress in plants. In our study, we identified the salt-tolerant rhizobacterium Pseudomonas psychrotolerans CS51. This species produces several plant-growth-promoting biochemicals like indole-3-acetic acid (33 ± 1.8 ng/mL) and gibberellic acid (GA3; 38 ± 1.3 and GA4; 23 ± 1.2 ng/mL) in Luria-Bertani(LB) media, and LB media spiked with 200 mM NaCl (indole-3-acetic acid(IAA); 17.6 ± 0.4 ng/mL, GA3; 21 ± 0.9 and GA4; 19 ± 1.0 ng/mL). In the current study, we aimed to investigate the effect of isolate CS51 and exogenous silicon (3 mM) on maize under salinity stress (200 mM). Our results showed that the sole application of isolate CS51, Si, and combined CS51 + Si significantly enhanced maize biomass and chlorophyll content under normal and salinity stress. Phytohormonal results showed that salinity stress increased abscisic acid (ABA; three folds) and jasmonic acid (JA; 49.20%). However, the sole and combined isolate CS51 + Si application markedly reduced ABA (1.5 folds) and JA content (14.89%). Besides, the sole and isolate CS51 + Si co-application strengthened the antioxidant system, such as flavonoid (97%) and polyphenol (19.64%), and lowered the proline content (57.69%) under NaCl stress. Similarly, the CS51 and Si inoculation (solely or combined) significantly enhanced the Si uptake (4 folds) and reduced the Na+ uptake (42.30%) in maize plants under NaCl stress. In conclusion, the current finding suggests that combining CS51 with Si can be used against salinity stress in maize plants and may be commercialized as a biofertilizer.

Cadmium stress significantly decreases agricultural productivity worldwide. Plant growth-promoting rhizobacteria (PGPR) are eco-friendly and inexpensive tool for mitigating heavy metal stress in crops. We isolated rhizospheric bacteria and screened them for various plant growth-promoting (PGP) traits as well as Cd tolerance. Only 6 bacterial isolates out of 55 assessed showed multiple PGP traits in response to different Cd concentrations. The Bacillus cereus ALT1 strain showed high tolerance to increased Cd amounts in the culture medium, while secreting indole-3-acetic acid (IAA) and organic acids into the culture medium. High Cd concentrations (0.7 mM, 1.4 mM, and 2.1 mM) reduced soybean shoot and root length, root/shoot fresh and dry weight, as well as chlorophyll content; however, inoculation with the bacterial isolate ALT1 mitigated Cd stress and enhanced both soybean growth parameters and chlorophyll content. It also decreased abscisic acid (ABA) amounts, enhanced salicylic acid (SA) production, and promoted antioxidant response by increasing total proteins (TP) and superoxide dismutase (SOD), while decreasing glutathione (GSH) content, lipid peroxidation (LPO), peroxidase (POD), superoxide anion (SOA), and polyphenol oxidase (PPO) in soybean plants. In addition, inductively coupled plasma mass spectrometry (ICP-MS) showed that soybean plants treated with the bacterial isolate ALT1 enhanced K uptake and decreased Cd amounts in comparison to control plants. The present study reveals that Cd-tolerant bacterial isolate ALT1 can alleviate Cd toxicity on plants by increasing their growth, thus imposing itself as an eco-friendly bio-fertilizer under Cd stress.