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1.
Gland Surg ; 13(6): 1045-1053, 2024 Jun 30.
Article in English | MEDLINE | ID: mdl-39015724

ABSTRACT

Background: Coronavirus disease 19 (COVID-19) has played a pivotal role in changing medical care around the world. During the pandemic, the operating rooms (ORs) were closed to elective surgery. Since breast cancer surgery is not regarded as an emergent procedure, there was an adoption of treatment regimen modification due to delays in treatment. Therefore, a decision was made to bridge early-stage HER2-positive breast cancer patients with neoadjuvant treatment to postpone surgery. Consequently, to reduce the frequency of dosing and the number of visits, as well as avoid steroid premedication, these patients were treated with ado-trastuzumab emtansine (T-DM1) every three weeks as opposed to weekly taxol and herceptin (TH). Case Description: Five patients with early-stage HER2-positive cancer were treated with neoadjuvant T-DM1 3.6 mg/kg IV every three weeks. Three of the five patients developed cancer progression identified by their physical exam and/or imaging. T-DM1 was discontinued, and all three patients underwent immediate surgery. The remaining two patients, 4 and 5, had a complete and partial pathological response, respectively. All five patients received adjuvant therapy after surgery, and currently, none of these patients show evidence of disease on follow-up. Conclusions: Our findings underscore the obstacles and treatment challenges encountered during the COVID-19 pandemic while preventing the spread of the virus and cancer progression. Furthermore, the use of T-DM1 for neoadjuvant treatment remains controversial, particularly when T-DM1 is used as a bridge to surgery during critical times. Perhaps better patient selection or a different drug regimen could have resulted in a better outcome in our study.

2.
PNAS Nexus ; 3(5): pgae148, 2024 May.
Article in English | MEDLINE | ID: mdl-38983693

ABSTRACT

The response of metals and their microstructures under extreme dynamic conditions can be markedly different from that under quasistatic conditions. Traditionally, high strain rates and shock stresses are achieved using cumbersome and expensive methods such as the Kolsky bar or large spall experiments. These methods are low throughput and do not facilitate high-fidelity microstructure-property linkages. In this work, we combine two powerful small-scale testing methods, custom nanoindentation, and laser-driven microflyer (LDMF) shock, to measure the dynamic and spall strength of metals. The nanoindentation system is configured to test samples from quasistatic to dynamic strain-rate regimes. The LDMF shock system can test samples through impact loading, triggering spall failure. The model material used for testing is magnesium alloys, which are lightweight, possess high-specific strengths, and have historically been challenging to design and strengthen due to their mechanical anisotropy. We adopt two distinct microstructures, solutionized (no precipitates) and peak-aged (with precipitates) to demonstrate interesting upticks in strain-rate sensitivity and evolution of dynamic strength. At high shock-loading rates, we unravel an interesting paradigm where the spall strength vs. strain rate of these materials converges, but the failure mechanisms are markedly different. Peak aging, considered to be a standard method to strengthen metallic alloys, causes catastrophic failure, faring much worse than solutionized alloys. Our high-throughput testing framework not only quantifies strength but also teases out unexplored failure mechanisms at extreme strain rates, providing valuable insights for the rapid design and improvement of materials for extreme environments.

3.
Sci Rep ; 14(1): 15774, 2024 Jul 09.
Article in English | MEDLINE | ID: mdl-38982193

ABSTRACT

In recent years, regulatory agencies have raised concerns about the presence of potentially carcinogenic substances in certain formulations of Angiotensin Receptor Blockers (ARBs). Specifically, nitrosamines and azido compounds have been identified in some ARB products. Nitrosamines are known to have carcinogenic properties and are associated with an increased risk of neoplasms. Spontaneous safety reports from the EudraVigilance Data Analysis System (EVDAS) database were analyzed to investigate cases of neoplasms associated with ARBs. A disproportionality analysis was conducted, calculating the reporting odds ratio (ROR) and 95% confidence intervals (CIs) using a case/non-case approach for each ARB drug. The EVDAS database contained 68,522 safety reports related to ARBs (including Azilsartan, Candesartan, Irbesartan, Olmesartan, Losartan, Valsartan, and Telmisartan), among which 3,396 (5%) cases were associated with neoplasms. The majority of these cases were reported in Germany (11.9%), followed by France (9.7%). Approximately 70% of the reports were submitted by healthcare professionals such as physicians and nurses. Among the ARBs, valsartan had the highest ROR for neoplasm (ROR 1.949, 95% CI 1.857-2.046). This association remained significant when comparing ARBs with other classes of antihypertensive drugs, including ACE inhibitors, beta-blockers, calcium channel blockers, and diuretics. Our study identifies a possible signal of an association between ARBs, particularly valsartan, and the risk of neoplasms. However, further observational and analytical studies are necessary to confirm these findings and elucidate the underlying mechanisms.


Subject(s)
Angiotensin Receptor Antagonists , Neoplasms , Humans , Neoplasms/drug therapy , Neoplasms/epidemiology , Angiotensin Receptor Antagonists/adverse effects , Angiotensin Receptor Antagonists/therapeutic use , Male , Retrospective Studies , Female , Middle Aged , Aged , Valsartan , Adult , Databases, Factual , Germany/epidemiology
4.
J Indian Soc Periodontol ; 28(1): 79-83, 2024.
Article in English | MEDLINE | ID: mdl-38988961

ABSTRACT

Background: Nonsurgical periodontal therapy results in the formation of a smear layer which inhibits tissue regeneration. Root biomodification (RB) using various agents has been tried for the enhancement of new attachment formation. However, no substantial therapeutic advantages of currently available root conditioning agents have been reported emphasizing the need for additional biologically acceptable agents. Glycolic acid (GA) due to its antimicrobial nature and ability of initiation and proliferation of fibroblasts may potentially modify root surface enabling regeneration. Materials and Methods: Eighty specimens from 40 single-rooted teeth were treated with 17% ethylenediaminetetraacetic acid (EDTA) and 5% GA and scanning electron microscopy analysis was done. The micrographs were examined for the evaluation of smear layer removal, total number of dentinal tubules, total number of patent dentinal tubules, mean diameter and surface area of dentinal tubules, and dentin erosion. Statistical analysis was done using unpaired t-test for intergroup comparison. Results: The efficacy of smear layer removal (P = 0.01) and dentin erosion (P = 0.042) was significantly better in the GA group. Both the groups showed no difference in dentinal tubule-related parameters. Conclusion: GA showed improved RB with greater smear layer removal and lesser dentin erosion, indicating its use as a potent alternative to the conventional EDTA root conditioning.

5.
Heliyon ; 10(13): e33217, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39027501

ABSTRACT

Background: Diabetic nephropathy represents a significant microvascular complication of diabetes, characterized by extracellular matrix accumulation, loss of cell-cell junctions, microalbuminuria, and diminished creatinine clearance. Despite its prevalence, therapeutic options dedicated to this condition are currently lacking. Natural products like bioflavonoids have garnered attention for their potential therapeutic benefits. The present study aimed to evaluate the efficacy of a bioflavonoid combination, including ginger extract, soy extract, and hesperetin, in a diabetic rat model. Methods: Diabetes was initiated in the rat pups via intraperitoneal injection of streptozotocin on the fifth postnatal day. After six weeks, rats exhibiting blood sugar levels exceeding 160 mg/dL were allocated into diabetic control and treatment groups, with eight animals each. A subset of rats received citrate buffer as a control. The treatment group received the bioflavonoid combination orally for twenty-four weeks. Various parameters, including glycemic levels, urinary parameters, antioxidant status, mRNA expression via Western blot, gel zymography, and immunohistochemistry, were assessed at the study's conclusion. Results: The bioflavonoid combination demonstrated significant reductions in hyperglycemia and various urinary parameters compared to controls. Notably, it modulated MMP-9/TIMP-1 expression, upregulated GLUT-4, and downregulated TGF-ß. Additionally, the combination enhanced total antioxidant capacity, indicating potential antioxidative benefits. Conclusions: This study highlights the therapeutic potential of a bioflavonoid combination (ginger extract, soy extract, and hesperetin) in improving renal function in diabetic nephropathy. By modulating key factors such as MMP-9/TIMP-1, TGF-ß, and GLUT-4, this combination presents a promising avenue for further exploration in managing diabetic nephropathy. These findings underscore the importance of natural products as potential therapeutic agents in addressing diabetic complications.

6.
Article in English | MEDLINE | ID: mdl-38944415

ABSTRACT

Corynebacterium glutamicum ATCC 13032 is a promising microbial chassis for industrial production of valuable compounds, including aromatic amino acids derived from the shikimate pathway. In this work, we developed two whole-cell, transcription factor based fluorescent biosensors to track cis,cis-muconic acid (ccMA) and chorismate in C. glutamicum. Chorismate is a key intermediate in the shikimate pathway from which value-added chemicals can be produced, and a shunt from the shikimate pathway can divert carbon to ccMA, a high value chemical. We transferred a ccMA-inducible transcription factor, CatM, from Acinetobacter baylyi ADP1 into C. glutamicum and screened a promoter library to isolate variants with high sensitivity and dynamic range to ccMA by providing benzoate, which is converted to ccMA intracellularly. The biosensor also detected exogenously supplied ccMA, suggesting the presence of a putative ccMA transporter in C. glutamicum, though the external ccMA concentration threshold to elicit a response was 100-fold higher than the concentration of benzoate required to do so through intracellular ccMA production. We then developed a chorismate biosensor, in which a chorismate inducible promoter regulated by natively expressed QsuR was optimized to exhibit a dose-dependent response to exogenously supplemented quinate (a chorismate precursor). A chorismate-pyruvate lyase encoding gene, ubiC, was introduced into C. glutamicum to lower the intracellular chorismate pool, which resulted in loss of dose dependence to quinate. Further, a knockout strain that blocked the conversion of quinate to chorismate also resulted in absence of dose dependence to quinate, validating that the chorismate biosensor is specific to intracellular chorismate pool. The ccMA and chorismate biosensors were dually inserted into C. glutamicum to simultaneously detect intracellularly produced chorismate and ccMA. Biosensors, such as those developed in this study, can be applied in C. glutamicum for multiplex sensing to expedite pathway design and optimization through metabolic engineering in this promising chassis organism. ONE-SENTENCE SUMMARY: High-throughput screening of promoter libraries in Corynebacterium glutamicum to establish transcription factor based biosensors for key metabolic intermediates in shikimate and ß-ketoadipate pathways.


Subject(s)
Biosensing Techniques , Chorismic Acid , Corynebacterium glutamicum , Sorbic Acid , Corynebacterium glutamicum/metabolism , Corynebacterium glutamicum/genetics , Biosensing Techniques/methods , Sorbic Acid/metabolism , Sorbic Acid/analogs & derivatives , Chorismic Acid/metabolism , Transcription Factors/genetics , Transcription Factors/metabolism , Promoter Regions, Genetic , Bacterial Proteins/genetics , Bacterial Proteins/metabolism , Acinetobacter/metabolism , Acinetobacter/genetics
7.
JCO Glob Oncol ; 10: e2300165, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38843471

ABSTRACT

PURPOSE: AML is a heterogeneous hematologic malignancy. Region-specific recommendations for AML management can enhance patient outcomes. This article aimed to develop recommendations for the Gulf Cooperation Council (GCC) countries. METHODS: Ten AML panel members from Kuwait, Oman, Qatar, and the United Arab Emirates (KOQU) participated in a modified two-round Delphi process. The panel first identified the unmet regional needs and finalized a list of core variables. Next, they voted on iterative statements drawn from international recommendations and provided feedback via a questionnaire. Consensus voting ≤70% was discussed, and additional clinical decision making statements were suggested. At round closure, a consensus vote took place on revised statements. RESULTS: The panel reached ≥97.8% consensus on AML management. The panel agreed to use international risk stratification categories for personalized treatment of AML. The presence of ≥10% blasts for recurrent genetic abnormalities was required for a diagnosis of AML. Key consensus was reached for different treatment stages. The panel noted that older patients pose a challenge because of poor cytogenetics and genetic anomalies and require different treatment approaches. The panel recommended venetoclax-hypomethylating agents; fludarabine, cytarabine, idarubicin, and granulocyte colony-stimulating factor; and targeted therapy for AML relapsed/refractory disease. Supportive care is considered on the basis of prevailing organisms and drug resistance. CONCLUSION: The GCC KOQU's consensus-based recommendations for managing AML include an evidence-based and region-specific framework.


Subject(s)
Consensus , Leukemia, Myeloid, Acute , Humans , Leukemia, Myeloid, Acute/therapy , United Arab Emirates/epidemiology , Delphi Technique , Practice Guidelines as Topic , Qatar/epidemiology , Kuwait/epidemiology
8.
J Alzheimers Dis Rep ; 8(1): 903-922, 2024.
Article in English | MEDLINE | ID: mdl-38910936

ABSTRACT

Background: Despite intense investigations, no effective treatment is yet available to reduce plaques and protect memory and learning in patients with Alzheimer's disease (AD), the most common neurodegenerative disorder. Therefore, it is important to identify a non-toxic, but effective, treatment option for AD. Objective: Cinnamein, a nontoxic compound, is naturally available in Balsam of Peru and Tolu Balsam. We examined whether cinnamein treatment could decrease plaques and improve cognitive functions in 5XFAD mouse model of AD. Methods: We employed in silico analysis, time-resolved fluorescence energy transfer assay, thermal shift assay, primary neuron isolation, western blot, immunostaining, immunohistochemistry, Barnes maze, T maze, and open field behavior. Results: Oral administration of cinnamein led to significant reduction in amyloid-ß plaque deposits in the brain and protection of spatial learning and memory in 5XFAD mice. Peroxisome proliferator-activated receptor alpha (PPARα), a nuclear hormone receptor, is involved in plaque lowering and increase in hippocampal plasticity. While investigating underlying mechanisms, we found that cinnamein served as a ligand of PPARα. Accordingly, oral cinnamein upregulated the level of PPARα, but not PPARß, in the hippocampus, and remained unable to decrease plaques from the hippocampus and improve memory and learning in 5XFAD mice lacking PPARα. While A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) is one of the drivers of nonamyloidogenic pathway, transcription factor EB (TFEB) is considered as the master regulator of autophagy. Cinnamein treatment was found to upregulate both ADAM10 and TFEB in the brain of 5XFAD mice via PPARα. Conclusions: Our results suggest that this balsam component may have therapeutic importance in AD.

10.
Top Cogn Sci ; 2024 Jun 24.
Article in English | MEDLINE | ID: mdl-38923214

ABSTRACT

The necessity for introducing interactionist and parallelism approaches in different branches of cognitive science emerged as a reaction to classical sequential stage-based models. Functional psychological models that emphasized and explained how different components interact, dynamically producing cognitive and perceptual states, influenced multiple disciplines. Chiefly among them were experimental psycholinguistics and the many applied areas that dealt with humans' ability to process different types of information in different contexts. Understanding how bilinguals represent and process verbal and visual input, how their neural and psychological states facilitate such interactions, and how linguistic and nonlinguistic processing overlap, has now emerged as an important area of multidisciplinary research. In this article, we will review available evidence from different language-speaking groups of bilinguals in India with a focus on situational context. In the discussion, we will address models of language processing in bilinguals within a cognitive psychological approach with a focus on existent models of inhibitory control. The paper's stated goal will be to show that the parallel architecture framework can serve as a theoretical foundation for examining bilingual language processing and its interface with external factors such as social context.

11.
Org Biomol Chem ; 22(25): 5087-5092, 2024 06 26.
Article in English | MEDLINE | ID: mdl-38835316

ABSTRACT

We have devised a supported-amine-catalyzed efficient synthesis of spiro-thiazolone-tetrahydrothiophenes via a sulfa-Michael/aldol cascade approach. The catalyst demonstrated sustained efficacy over 21 cycles. These derivatives were found to exhibit excellent binding abilities with purified human serum albumin as indicated by both in silico and in vitro-based experiments.


Subject(s)
Amines , Thiophenes , Humans , Catalysis , Thiophenes/chemistry , Thiophenes/chemical synthesis , Amines/chemistry , Amines/chemical synthesis , Serum Albumin, Human/chemistry , Serum Albumin, Human/metabolism , Protein Binding , Spiro Compounds/chemistry , Spiro Compounds/chemical synthesis , Molecular Structure , Thiazoles/chemistry , Thiazoles/chemical synthesis , Molecular Docking Simulation
12.
Sensors (Basel) ; 24(11)2024 May 25.
Article in English | MEDLINE | ID: mdl-38894193

ABSTRACT

The growing demand for agricultural output and limited resources encourage precision applications to generate higher-order output by utilizing minimal inputs of seed, fertilizer, land, and water. An electronically operated planter was developed, considering problems like ground-wheel skidding, field vibration, and the lack of ease in field adjustments of ground-wheel-driven seed-metering plates. The seed-metering plate of each unit of the developed planter is individually driven by a brushless direct current (BLDC) motor, and a BLDC motor-based aspirator is attached for pneumatic suction of seeds. The revolutions per minute (RPM) of the seed-metering plate are controlled by a microcontroller as per the received data relating to RPM from the ground wheel and the current RPM of the seed-metering plate. A feedback loop with proportional integral derivative (PID) control is responsible for reducing the error. Additionally, each row unit is attached to a parallelogram-based depth control system that can provide depth between 0 and 100 mm. The suction pressure in each unit is regulated as per seed type using the RPM control knob of an individual BLDC motor-based aspirator. The row-to-row spacing can be changed from 350 mm to any desired spacing. The cotton variety selected for the study was RCH 659, and the crucial parameters like orifice size, vacuum pressure, and forward speed were optimized in the laboratory with the adoption of a central composite rotatable design. An orifice diameter of 2.947 mm with vacuum pressure of 3.961 kPa and forward speed of 4.261 km/h was found optimal. A quality feed index of 93% with a precision index of 8.01% was observed from laboratory tests under optimized conditions. Quality feed index and precision index values of 88.8 and 12.75%, respectively, were obtained from field tests under optimized conditions.

13.
Poult Sci ; 103(7): 103815, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38713988

ABSTRACT

The objective of this study was to evaluate the effect of 25% arginine supplementation as a functional amino acid in partially alleviating the detrimental effects of necrotic enteritis (NE) on the growth performance, serum biochemistry, gut integrity, and the relative gene expression of tight junction proteins and inflammatory cytokines in broilers during NE. Three hundred and sixty 1-day-old chicks were randomly allocated to 4 treatments in a 2 × 2 factorial arrangement -basal diet and 125% arginine diet, with or without NE challenge. NE was induced by inoculating 1 × 104Eimeria maxima sporulated oocysts on d 14 and 1 × 108 CFU/bird C. perfringens on d 19, 20, and 21. The NE challenge had a significant effect on the BWG (p < 0.05), FCR (p < 0.05), serum AST (p < 0.05), GLU (p < 0.05), and K+ (p < 0.05) levels, and intestinal permeability (p < 0.05) and jejunal lesion score (p < 0.05). A significant challenge × diet interaction effect was observed in the cecal tonsil CD8+: CD4+ T-cell ratio on d 21 (p < 0.05) and 28 (p < 0.05) and spleen CD8+: CD4+ T-cell ratio on d 21 (p < 0.05) and 35 (p < 0.05). Arginine supplementation significantly increased the CD8+: CD4+ T-cell ratio in uninfected birds but decreased the CD8+: CD4+ T-cell ratio in infected birds. On d 21, a significant interaction effect was observed on the relative expression of the iNOS gene (p < 0.05). Arginine supplementation significantly downregulated the expression of the iNOS gene in infected birds. A significant effect of the challenge (p < 0.05) was observed on the relative gene expression of the ZO-1 gene in the jejunum. NE challenge significantly downregulated the expression of the ZO-1 gene on d 21. In conclusion, arginine supplementation did not alleviate the depression in growth performance and disease severity during the NE challenge. However, arginine downregulated the expression of inflammatory cytokines and enzymes, preventing inflammatory injury to the tissues during NE. Hence, arginine might be supplemented with other alternatives to downregulate inflammatory response during NE in poultry.


Subject(s)
Animal Feed , Arginine , Chickens , Coccidiosis , Diet , Dietary Supplements , Enteritis , Intestines , Poultry Diseases , Random Allocation , Animals , Arginine/administration & dosage , Arginine/pharmacology , Chickens/growth & development , Chickens/immunology , Poultry Diseases/immunology , Dietary Supplements/analysis , Enteritis/veterinary , Enteritis/immunology , Animal Feed/analysis , Diet/veterinary , Coccidiosis/veterinary , Coccidiosis/immunology , Intestines/drug effects , Eimeria/physiology , Clostridium perfringens/physiology , Male , Clostridium Infections/veterinary , Clostridium Infections/immunology
14.
Poult Sci ; 103(7): 103826, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38761462

ABSTRACT

The objective of this study was to evaluate the effects of 25% and 35% arginine supplementation in partially alleviating the effects of necrotic enteritis (NE) challenge on the production performance, intestinal integrity, and relative gene expression of tight junction proteins and inflammatory cytokines in broilers. Four hundred and eighty 1-day-old chicks were randomly allocated to the 4 treatments- Uninfected + Basal, NE + Basal, NE + Arg 125%, and NE + Arg 135%. NE was induced by inoculating 1 × 104Eimeria maxima sporulated oocysts on d 14 and 1 × 108 CFU/bird C. perfringens on d 19, 20, and 21 of age by oral gavage. The NE challenge significantly decreased body weight gain (BWG) (p < 0.05) and increased the feed conversion ratio (FCR) (p < 0.05). On d 21, the NE challenge also increased the jejunal lesion score (p < 0.05) and relative gene expression of IL-10 and decreased the expression of the tight junction proteins occludin (p < 0.05) and claudin-4 (p < 0.05). The 125% arginine diet significantly increased intestinal permeability (p < 0.05) and the relative gene expression of iNOS (p < 0.05) and IFN-γ (p < 0.05) on d 21 and the bile anti-C. perfringens IgA concentration by 39.74% (p < 0.05) on d 28. The 135% arginine diet significantly increased the feed intake during d 0 - 28 (p < 0.05) and 0 to 35 (p < 0.05) and increased the FCR on d 0 to 35 (p < 0.05). The 135% and 125% arginine diet increased the spleen CD8+: CD4+ T-cell ratio on d 28 (p < 0.05) and 35 (p < 0.05), respectively. The 135% arginine diet increased the CT CD8+:CD4+ T-cell ratio on d 35 (p < 0.05). In conclusion, the 125% and 135% arginine diets did not reverse the effect of the NE challenge on the growth performance. However, the 125% arginine diet significantly increased the cellular and humoral immune response to the challenge. Hence, the 125% arginine diet could be used with other feed additives to improve the immune response of the broilers during the NE challenge.


Subject(s)
Animal Feed , Arginine , Chickens , Clostridium perfringens , Coccidiosis , Diet , Dietary Supplements , Enteritis , Poultry Diseases , Random Allocation , Animals , Chickens/growth & development , Chickens/immunology , Arginine/administration & dosage , Arginine/pharmacology , Poultry Diseases/immunology , Poultry Diseases/microbiology , Enteritis/veterinary , Enteritis/immunology , Animal Feed/analysis , Diet/veterinary , Dietary Supplements/analysis , Clostridium perfringens/physiology , Coccidiosis/veterinary , Coccidiosis/immunology , Eimeria/physiology , Intestines/drug effects , Clostridium Infections/veterinary , Clostridium Infections/immunology , Dose-Response Relationship, Drug , Male , Immunity, Innate/drug effects
15.
3 Biotech ; 14(6): 153, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38742228

ABSTRACT

Genus Ophiorrhiza has recently emerged as one of the promising sources of Camptothecin (CPT), an antitumour monoterpene indole alkaloid. It possesses CPT in its every part and has a relatively short life span. To determine whether differentiation plays any role in the synthesis and/or accumulation of CPT, the concentration of CPT was analyzed across various tissues of Ophiorrhiza rugosa var. decumbens obtained through both direct as well as indirect modes of regeneration. The results revealed that the plants obtained from both types of regeneration showed similar levels of CPT. It was also observed that with differentiation, the accumulation of CPT increases, as the callus, being an undifferentiated mass of cells, had only traces of CPT. In contrast, the completely differentiated in-vitro plant obtained from it showed a significantly higher percentage of CPT in shoots (0.22% dry weight) and roots (0.247% dw). The CPT when analyzed after hardening, varied among different organs of the plant. It was also observed that the inflorescence accumulated the highest concentration of CPT (0.348% dw) once the flowering began, accompanied by a decrease in remaining organs. This decrease may result from CPT being mobilized to the inflorescence as a chemical defense mechanism. These findings allowed us to determine the ideal plant harvesting age for CPT extraction. The findings could be used to decide the right stage of plant harvest, which is just before the onset of blooming. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-024-03999-4.

16.
Parkinsonism Relat Disord ; 124: 107010, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38772265

ABSTRACT

PURPOSE: We investigated the contribution of genomic data reanalysis to the diagnostic yield of dystonia patients who remained undiagnosed after prior genome sequencing. METHODS: Probands with heterogeneous dystonia phenotypes who underwent initial genome sequencing (GS) analysis in 2019 were included in the reanalysis, which was performed through gene-specific discovery collaborations and systematic genomic data reanalysis. RESULTS: Initial GS analysis in 2019 (n = 111) identified a molecular diagnosis in 11.7 % (13/111) of cases. Reanalysis between 2020 and 2023 increased the diagnostic yield by 7.2 % (8/111); 3.6 % (4/111) through focused gene-specific clinical correlation collaborative efforts [VPS16 (two probands), AOPEP and POLG], and 3.6 % (4/111) by systematic reanalysis completed in 2023 [NUS1 (two probands) and DDX3X variants, and a microdeletion encompassing VPS16]. Seven of these patients had a high phenotype-based dystonia score ≥3. Notable unverified findings in four additional cases included suspicious variants of uncertain significance in FBXL4 and EIF2AK2, and potential phenotypic expansion associated with SLC2A1 and TREX1 variants. CONCLUSION: GS data reanalysis increased the diagnostic yield from 11.7 % to 18.9 %, with potential extension up to 22.5 %. While optimal timing for diagnostic reanalysis remains to be determined, this study demonstrates that periodic re-interrogation of dystonia GS datasets can provide additional genetic diagnoses, which may have significant implications for patients and their families.


Subject(s)
Dystonia , Dystonic Disorders , Humans , Male , Female , Adult , Dystonic Disorders/genetics , Dystonic Disorders/diagnosis , Dystonia/genetics , Dystonia/diagnosis , Middle Aged , Young Adult , Whole Genome Sequencing , Adolescent , Child , Phenotype
17.
Cell Biochem Funct ; 42(4): e4037, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38736204

ABSTRACT

Diabetes mellitus is associated with secondary complications such as diabetic retinopathy (DR), nephropathy (DN), and cardiomyopathy (DCM), all of which significantly impact patient health. Intercellular adhesion molecule-1 (ICAM-1) has been implicated in inflammatory responses and endothelial dysfunction, both crucial in the pathogenesis of these complications. The goal of this review is to investigate at potential therapy methods that target ICAM-1 pathways and to better understand the multifaceted role of ICAM-1 in secondary diabetic problems. A meticulous analysis of scholarly literature published globally was conducted to examine ICAM-1involvement in inflammatory processes, endothelial dysfunction, and oxidative stress related to diabetes and its complications. Elevated ICAM-1 levels are strongly associated with augmented leukocyte adhesion, compromised microvascular function, and heightened oxidative stress in diabetes. These pathways contribute significantly to DR, DN, and DCM pathogenesis, highlighting ICAM-1 as a key player in their progression. Understanding ICAM-1 role in secondary diabetic complications offers insights into novel therapeutic strategies. Targeting ICAM-1 pathways may mitigate inflammation, improve endothelial function, and ultimately attenuate diabetic complications, thereby enhancing patient health outcomes. Continued research in this area is crucial for developing effective targeted therapies.


Subject(s)
Intercellular Adhesion Molecule-1 , Humans , Intercellular Adhesion Molecule-1/metabolism , Diabetes Complications/metabolism , Oxidative Stress , Animals , Diabetic Nephropathies/metabolism , Diabetic Nephropathies/pathology , Inflammation/metabolism , Diabetic Retinopathy/metabolism , Diabetic Retinopathy/pathology , Diabetic Retinopathy/etiology
18.
Front Microbiol ; 15: 1383989, 2024.
Article in English | MEDLINE | ID: mdl-38694800

ABSTRACT

We investigated antibiotic resistance pattern in clinical bacterial pathogens isolated from in-patients and out-patients, and compared it with non-clinical bacterial isolates. 475 bacterial strains isolated from patients were examined for antibiotic resistance. Staphylococcus spp. (148; 31.1%) were found to be the most prevalent, followed by Klebsiella pneumoniae (135; 28.4%), Escherichia coli (74; 15.5%), Pseudomonas aeruginosa (65; 13.6%), Enterobacter spp. (28; 5.8%), and Acinetobacter spp. (25; 5.2%). Drug-resistant bacteria isolated were extended spectrum-ß-lactamase K. pneumoniae (8.8%), E. coli (20%), metallo-ß-lactamase P. aeruginosa (14; 2.9%), erythromycin-inducing clindamycin resistant (7.4%), and methicillin-resistant Staphylococcus species (21.6%). Pathogens belonging to the Enterobacteriaceae family were observed to undergo directional selection developing resistance against antibiotics ciprofloxacin, piperacillin-tazobactam, cefepime, and cefuroxime. Pathogens in the surgical ward exhibited higher levels of antibiotic resistance, while non-clinical P. aeruginosa and K. pneumoniae strains were more antibiotic-susceptible. Our research assisted in identifying the drugs that can be used to control infections caused by antimicrobial resistant bacteria in the population and in monitoring the prevalence of drug-resistant bacterial pathogens.

19.
Sci Rep ; 14(1): 10525, 2024 05 08.
Article in English | MEDLINE | ID: mdl-38720057

ABSTRACT

The narrow zone of soil around the plant roots with maximum microbial activity termed as rhizosphere. Rhizospheric bacteria promote the plant growth directly or indirectly by providing the nutrients and producing antimicrobial compounds. In this study, the rhizospheric microbiota of peanut plants was characterized from different farms using an Illumina-based partial 16S rRNA gene sequencing to evaluate microbial diversity and identify the core microbiome through culture-independent (CI) approach. Further, all rhizospheric bacteria that could grow on various nutrient media were identified, and the diversity of those microbes through culture-dependent method (CD) was then directly compared with their CI counterparts. The microbial population profiles showed a significant correlation with organic carbon and concentration of phosphate, manganese, and potassium in the rhizospheric soil. Genera like Sphingomicrobium, Actinoplanes, Aureimonas _A, Chryseobacterium, members from Sphingomonadaceae, Burkholderiaceae, Pseudomonadaceae, Enterobacteriaceae family, and Bacilli class were found in the core microbiome of peanut plants. As expected, the current study demonstrated more bacterial diversity in the CI method. However, a higher number of sequence variants were exclusively present in the CD approach compared to the number of sequence variants shared between both approaches. These CD-exclusive variants belonged to organisms that are more typically found in soil. Overall, this study portrayed the changes in the rhizospheric microbiota of peanuts in different rhizospheric soil and environmental conditions and gave an idea about core microbiome of peanut plant and comparative bacterial diversity identified through both approaches.


Subject(s)
Arachis , Bacteria , Metagenomics , Microbiota , RNA, Ribosomal, 16S , Rhizosphere , Soil Microbiology , Arachis/microbiology , India , Microbiota/genetics , RNA, Ribosomal, 16S/genetics , Metagenomics/methods , Bacteria/genetics , Bacteria/classification , Bacteria/isolation & purification , Farms , Plant Roots/microbiology , Phylogeny , Metagenome , Biodiversity
20.
Semin Vasc Surg ; 37(1): 20-25, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38704179

ABSTRACT

Compression of the neurovascular structures at the level of the scalene triangle and pectoralis minor space is rare, but increasing awareness and understanding is allowing for the treatment of more individuals than in the past. We outlined the recognition, preoperative evaluation, and treatment of patients with neurogenic thoracic outlet syndrome. Recent work has illustrated the role of imaging and centrality of the physical examination on the diagnosis. However, a fuller understanding of the spatial biomechanics of the shoulder, scalene triangle, and pectoralis minor musculotendinous complex has shown that, although physical therapy is a mainstay of treatment, a poor response to physical therapy with a sound diagnosis should not preclude decompression. Modes of failure of surgical decompression stress the importance of full resection of the anterior scalene muscle and all posterior rib impinging elements to minimize the risk of recurrence of symptoms. Neurogenic thoracic outlet syndrome is a rare but critical cause of disability of the upper extremity. Modern understanding of the pathophysiology and evaluation have led to a sounder diagnosis. Although physical therapy is a mainstay, surgical decompression remains the gold standard to preserve and recover function of the upper extremity. Understanding these principles will be central to further developments in the treatment of this patient population.


Subject(s)
Decompression, Surgical , Thoracic Outlet Syndrome , Thoracic Outlet Syndrome/diagnosis , Thoracic Outlet Syndrome/physiopathology , Thoracic Outlet Syndrome/therapy , Thoracic Outlet Syndrome/surgery , Humans , Treatment Outcome , Predictive Value of Tests , Physical Therapy Modalities , Recovery of Function , Risk Factors , Physical Examination , Biomechanical Phenomena , Diagnostic Imaging/methods
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