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AIMS: The Lynch syndrome (LS) screening algorithm requires BRAF testing as a fundamental step to distinguish sporadic from LS-associated colorectal carcinomas (CRC). BRAF testing by immunohistochemistry (IHC) has shown variable results in the literature. Our aim was to analyse concordance between BRAFV600E IHC and BRAF molecular analysis in a large, mono-institutional CRC whole-slide, case series with laboratory validation. METHODS AND RESULTS: MisMatch repair (MMR) protein (hMLH1, hPMS2, hMSH2, and hMSH6) and BRAFV600E IHC were performed on all unselected cases of surgically resected CRCs (2018-2023). An in-house validation study for BRAFV600E IHC was performed in order to obtain optimal IHC stains. BRAFVV600E IHC was considered negative (score 0), positive (scores 2-3), and equivocal (score 1). Interobserver differences in BRAFV600E IHC scoring were noted in the first 150 cases prospectively collected. Nine-hundred and ninety CRCs cases (830 proficient (p)MMR/160 deficient (d)MMR) were included and all cases performed BRAFV600E IHC (BRAFV600E IHC-positive 13.5% of all series; 66.3% dMMR cases; 3.4% pMMR cases), while 333 also went to BRAF mutation analysis. Optimal agreement in IHC scoring between pathologists (P < 0.0001) was seen; concordance between BRAFV600E IHC and BRAF molecular analysis was extremely high (sensitivity 99.1%, specificity 99.5%; PPV 99.1%, and NPV 99.5%). Discordant cases were reevaluated; 1 score 3 + IHC/wildtype case was an interpretation error and one score 0 IHC/mutated case was related to heterogenous BRAFV600E IHC expression. Among the 12 IHC-equivocal score 1+ cases (which require BRAF molecular analysis), three were BRAF-mutated and nine BRAF-wildtype. CONCLUSION: BRAFV600E IHC can be used as a reliable surrogate of molecular testing after stringent in-house validation.
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Neoplasias Encefálicas , Neoplasias Colorretais Hereditárias sem Polipose , Neoplasias Colorretais , Síndromes Neoplásicas Hereditárias , Humanos , Neoplasias Colorretais Hereditárias sem Polipose/diagnóstico , Neoplasias Colorretais Hereditárias sem Polipose/genética , Imuno-Histoquímica , Proteínas Proto-Oncogênicas B-raf/genética , Proteínas Proto-Oncogênicas B-raf/metabolismo , Detecção Precoce de Câncer , Neoplasias Colorretais/diagnóstico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Técnicas de Diagnóstico Molecular , Algoritmos , Reparo de Erro de Pareamento de DNA , MutaçãoRESUMO
Zinc-solubilizing bacteria (ZSB) can convert insoluble zinc to an accessible form and increase Zn bioavailability in soil, which helps mitigate Zn deficiency in crops. In this study, different bacterial strains were screened for different Zn solubilization and plant growth promotion traits. Two bacterial strains, Acinetobacter pittii DJ55 and Stenotrophomonas maltophilia DJ24, were tested for their Zn-solubilizing potential on plate media, and both showed variable levels of Zn solubilization. The results showed that the bacterial strains applied to the plants in the pot experiment caused improvements in growth parameters compared to control conditions. DJ55, when applied with an insoluble source, enhanced plant height, leaf number, and leaf area compared to DJ24 and control conditions, while the maximum fruit weight was noticed in plants treated with ZnSO4. An increase in chlorophyll contents was noted in plants treated with ZnSO4, while maximum carotenoid contents were observed in plants treated with DJ55 + ZnO when compared with their controls. Plants supplemented with ZnO and DJ55 showed higher zinc content and iron content as compared to their respective controls. The expression patterns of the SLZIP5 and SLZIP4 genes were changed in the root and shoot. Application of ZnO stimulates both gene expression and protein synthesis in tomato roots and shoots. Inoculation of tomato plants with ZSB and insoluble ZnO reduced the expression of the SLZIP5 and SLZIP4 genes in the root and shoot. In conclusion, both strains can be considered as potential zinc-solubilizing bioinoculants to promote the growth and production yield of tomato.
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Solanum lycopersicum , Óxido de Zinco , Rizosfera , Proteínas de Membrana Transportadoras/genética , Bactérias , ZincoRESUMO
Illustrating the population structure and genetic diversity in selected germplasm resources (after three year multi locations trials) plays a key role which directly utilize the selection of lines in a population for accumulative trait breeding in crops. In order to further understand, the structure of population and genetic variability, we explored 100 selected lines, cultivated for three consecutive years (2016-2019) in swat, University of Malakand, Khyber Pakhtunkhwa Pakistan and Provinces of China (Chongqing and Beijing) with 33 mapped SSR markers. The integrated population structure analysis in a core of hundred germplasm with Pakistani origin with three approved commercial barley cultivars have strong stratification that allowed their division into four major subpopulations (i.e. PI, PII, PIII and PIV) and an admixture subpopulation, with 52, 9, 15 and 27 germplasm respectively. A total of 133 alleles were identified with mean value of 0.80 Polymorphic information content. The number of alleles detected by the system varied from two alleles amplified to as six with an average of 4.03 per SSR marker pair. The gene diversity ranged from 0.56 to 0.98 with an average of 0.82 in selected germplasm resources. Based on the SSR data, the 100 selected germplasm with three cultivars were classified into four main phylogenetic Linages (LI, LII, LIII and LIV) which corresponded to the phylogenic grouping in genotypes. We assembled a core set of 20 barley genotypes (~1/5 of original population size) to sustain sufficient mapping of SSR marker with Phenotype, in which we proposed four SSR markers, Bmac0040, Bmac0134, Bmag0125 and Bmag0211 for malt gene and marker (Bmac0399) for tolerance to salinity gene, which will be applicable for marker assisted breeding in barley gene resources.
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Variação Genética , Hordeum , Hordeum/genética , Paquistão , Filogenia , Repetições de Microssatélites/genética , Alelos , GenótipoRESUMO
Meckel's diverticulum is the most common gastrointestinal tract's congenital abnormality. Spontaneous perforation of Meckel's diverticulum is very rare and can mimic acute appendicitis. Here we report the case of an 11-year-old male patient, who was presented to the Surgical A unit of Ayub Teaching Hospital, Abbottabad on 21st January, 2021 with one-day history of abdominal pain, predominantly in the periumbilical area and right iliac fossa, associated with nausea. On physical examination his abdomen was tense, tender with guarding and generalized rigidity. A provisional diagnosis of perforated appendix or enteric perforation of a hollow viscus was made. The patient had an emergency laparotomy, where a perforated Meckel's diverticulum was discovered. Resection of the portion of gut containing Meckel's diverticulum was done along with primary anastomosis. Heterotopic gastric mucosa of diverticulitis, associated with perforation was confirmed on histopathology. The patient made an uneventful recovery during postoperative period. This case report is an interesting and an unusual case of Meckel's diverticulum complication. It highlights the importance of considering Meckel's diverticulum as a differential diagnosis in every patient presenting with acute abdomen in this age group.
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Abdome Agudo , Apendicite , Perfuração Intestinal , Divertículo Ileal , Masculino , Humanos , Criança , Divertículo Ileal/complicações , Divertículo Ileal/diagnóstico , Divertículo Ileal/cirurgia , Perfuração Espontânea/complicações , Perfuração Espontânea/cirurgia , Dor Abdominal/cirurgia , Abdome Agudo/etiologia , Abdome Agudo/cirurgia , Abdome Agudo/diagnóstico , Laparotomia/efeitos adversos , Perfuração Intestinal/etiologia , Perfuração Intestinal/cirurgia , Perfuração Intestinal/diagnóstico , Apendicite/cirurgiaRESUMO
BACKGROUND: Chemical fertilization helped modern agriculture in grain yield improvement to ensure food security. The response of chemical fertilization for higher hybrid rice production is highly dependent on optimal fertilization management in paddy fields. To assess such responses, in the current work we examine the yield, root growth, and expression of related genes responsible for stress metabolism of nitrogen (N) and phosphorus (P) in two hybrid-rice cultivars Deyou4727 (D47) and Yixiangyou2115 (Y21). METHODS AND RESULTS: The experiment followed four nitrogen (N) (N0, N60, N120, and N180 kg/ha) and phosphorus (P) (P0, P60, P90, and P120 kg/ha) fertilizer levels. The grain yield in D47 was more sensitive to nitrogen application, while Y21 was more sensitive to phosphorus application, which resulted in comparatively higher biomass and yield. Our findings were corroborated by gene expression studies of glutamine synthetase OsGS1;1 and OsGS1;2 and phosphate starvation-related genes PHR1 and SPX, confirming sensitivity to N and P application. The number of roots was less sensitive to nitrogen application in D47 between N0 and N60, but the overall nutrient response difference was significantly higher due to the deep rooting system as compared to Y21. CONCLUSIONS: The higher yield, high N and P use efficiency, and versatile root growth of D47 make it suitable to reduce unproductive usage of N and P from paddy fields, improving hybrid rice productivity, and environmental safety in the Sichuan basin area of China.
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Agricultura/métodos , Oryza/genética , Oryza/metabolismo , Biomassa , China , Fertilizantes/análise , Nitrogênio/metabolismo , Nutrientes , Fósforo/metabolismo , Raízes de Plantas/metabolismo , SoloRESUMO
The ethnic groups that inhabit the mountainous Dir and Swat districts of northern Pakistan are marked by high levels of cultural and phenotypic diversity. To obtain knowledge of the extent of genetic diversity in this region, we investigated Y-chromosomal diversity in five population samples representing the three main ethnic groups residing within these districts, including Gujars, Pashtuns and Kohistanis. A total of 27 Y-chromosomal short tandem repeats (Y-STRs) and 331 Y-chromosomal single nucleotide polymorphisms (Y-SNPs) were investigated. In the Y-STRs, we observed very high and significant levels of genetic differentiation in nine of the 10 pairwise between-group comparisons (RST 0.179-0.746), and the differences were mirrored in the Y-SNP haplogroup frequency distribution. No genetic differences were found between the two Pashtun subethnic groups Tarklanis and Yusafzais (RST = 0.000). Utmankhels, also considered Pashtuns culturally, were not closely related to any of the other population samples (RST 0.451-0.746). Thus, our findings provide examples of both associations and dissociations between cultural and genetic legacies. When analyzed within a larger continental-scale context, these five ethnic groups fall mostly outside the previously characterized Y-chromosomal gene pools of the Indo-Pakistani subcontinent. Male founder effects, coupled with culturally and topographically based constraints upon marriage and movement, are likely responsible for the high degree of genetic structure in this region.
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Cromossomos Humanos Y/genética , Etnicidade/genética , Genética Populacional , Efeito Fundador , Haplótipos , Humanos , Masculino , Repetições de Microssatélites , Paquistão , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Valvular heart disease (VHD) is an active process involving a wide range of pathological changes. The major complications of VHD are stenosis and regurgitation, which are macroscopic phenomena, induced in part through cellular changes. Altered expression of mitochondria associated genes causes membrane potential depolarization, leading to the increased levels of apoptosis observed in cardiac dysfunction. Objective of this study is to find molecular medicine candidates that can control expression of the key mitochondria apoptosis regulatory genes. Present study aims to assess the way microRNA are involved in regulating mitochondrial apoptosis regulatory genes and observation of their expression in the heart valve dysfunction. Apoptotic genes PUMA and DRP1 were found to be highly expressed, whereas anti-apoptotic gene ARC was down regulated. The expression level of GATA-4 transcription factor was also reduced in cardiac valve tissues. MicroRNAs miR-15a and miR-29a were repressed, while miR-214 was up regulated. Furthermore, study showed that PUMA, DRP1 and ARC expression might be attenuated by their respective miRNAs. Our results indicate that mitochondria regulatory genes might be controlled by miR-15a, miR-29a and miR-214, in VHD patients. Present study may provide platform for future research regarding potential therapeutic role of miRNAs in CVDs.
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Insuficiência da Valva Aórtica/genética , MicroRNAs/genética , Mitocôndrias/metabolismo , Insuficiência da Valva Mitral/genética , Adulto , Animais , Animais Recém-Nascidos , Insuficiência da Valva Aórtica/metabolismo , Insuficiência da Valva Aórtica/patologia , Insuficiência da Valva Aórtica/cirurgia , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proteínas do Citoesqueleto/genética , Proteínas do Citoesqueleto/metabolismo , Dinaminas , Feminino , Fator de Transcrição GATA4/genética , Fator de Transcrição GATA4/metabolismo , GTP Fosfo-Hidrolases/genética , GTP Fosfo-Hidrolases/metabolismo , Regulação da Expressão Gênica , Humanos , Masculino , MicroRNAs/metabolismo , Proteínas Associadas aos Microtúbulos/genética , Proteínas Associadas aos Microtúbulos/metabolismo , Mitocôndrias/patologia , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Insuficiência da Valva Mitral/metabolismo , Insuficiência da Valva Mitral/patologia , Insuficiência da Valva Mitral/cirurgia , Miócitos Cardíacos/citologia , Miócitos Cardíacos/metabolismo , Proteínas do Tecido Nervoso/genética , Proteínas do Tecido Nervoso/metabolismo , Cultura Primária de Células , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , Ratos , Transdução de Sinais , Substituição da Valva Aórtica TranscateterRESUMO
Muslims practice fasting during the ''holy month of Ramadan'', which poses special difficulties for those who have diabetes. Studies show that a sizable fraction of people with type 1 and type 2 diabetes fast despite the health hazards that come with the condition. This indicates that the incidence of diabetes among Muslims who fast is noteworthy. An increased vulnerability to acute problems, such as hypoglycemia, hyperglycemia, and diabetic ketoacidosis, is caused by extended fasting periods, irregular eating and sleeping routines, and changes in medication regimens. Healthcare professionals (HCPs), especially General Practitioners (GPs), should be involved in advising patients on safe fasting practices to strike a balance between religious observance and medical guidance. While guidelines from groups such as the Diabetes and Ramadan International Alliance and the International Diabetes Federation provide helpful suggestions, GPs are responsible for ensuring patient safety during Ramadan, particularly in areas where access to diabetes specialists is restricted. GPs are essential in managing diabetes-related issues before and throughout Ramadan, as well as in providing organized education and increasing awareness. A GP's primary responsibility at this time is to oversee the timely referral of high-risk patients and to effectively communicate with patients. To increase public awareness and support for diabetes care during Ramadan, it is also advised to work with religious leaders and make use of social media channels. It is ultimately in line with medical and religious beliefs to prioritize diabetes treatment during Ramadan, emphasizing the critical role general practitioners play in preserving the health and well-being of diabetics who are fasting.
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Berberine hydrochloride (BH) has long been known for its therapeutic efficacy. In the present study, we aimed to treat mice with colitis using dung beetle chitosan (DCS) -transported BH. To achieve this, BH-loaded DCS/sodium alginate microspheres (SA-DCS-BH) were prepared. The SA-DCS-BH was characterized using SEM, DLS, FT-IR, and XRD, then was used for administration and anti-inflammatory examination in mice. SEM and DLS confirmed the surface morphology of the microspheres, and the particle size was relatively uniform. FT-IR and XRD results confirmed that BH was successfully loaded. In vitro and in vivo studies showed that SA-DCS-BH had slow-release ability. After treatment with SA-DCS-BH, DAI was significantly reduced, colon weight and length increased, spleen length and weight reduced, concentrations of pro-inflammatory cytokines in colonic tissues were reduced, and gut microbiota species abundance was modulated. In addition, this study found a correlation between specific microbes and colitis indicators, Muribaculaceae showed sequential growth after receiving BH, SA-CS-BH, and SA-DCS-BH treatments, respectively. It was concluded that SA-DCS-BH effectively delivered the BH to the intestine with slow-release ability and exhibited anti-inflammatory effects by immune response. Compared to commercial chitosan, DCS has potential for modulating intestinal microorganisms and more suitable carrier for intestinal drug delivery systems.
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Berberina , Quitosana , Colite , Camundongos , Animais , Quitosana/farmacologia , Berberina/farmacologia , Microesferas , Espectroscopia de Infravermelho com Transformada de Fourier , Colite/induzido quimicamente , Colite/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Alginatos/farmacologia , ColoRESUMO
Tin monoxide is a significant functional semiconductor material which employed to a wide area of applications especially optical and energy storage devices. Presently, template free hydrothermal technique has been employing to synthesize stannous oxide (SnO) clinopinacoid type controlled morphology using SnCl2 x 2H2O, NH3, and H2O as raw materials. The crystalline phase, morphology, particle size and component were characterized by X-ray diffraction (XRD), energy-dispersive X-ray spectroscopy (EDS) and field-emission scanning electron microscopy (FESEM). FESEM results exhibited the large scale homogeneous growth of clinopinacoid architecture with the obvious size of 5 - 7 micrometers. The XRD results showed that the average crystallite size of the tetragonal phase romarchite SnO was about 29 nm calculated from the FWHM of X-ray diffraction pattern. The dominant Raman active modes A(1g) = 205 cm(-1), B(1g) = 105-107 cm(-1) and about 6 cm(-1) redshift were observed by the Raman spectroscopy, which further confirmed the existence of the nano tetragonal phase SnO. The electrochemical performance of as-synthesized SnO clinopinacoid structure as the anode material for lithium ion batteries was investigated. It was observed that the first discharge capacity of the two samples could reach a very high value of 1502 mA h g(-1) and 1422 mA h g(-1) respectively. The effect of nitrogen concentration on morphology as well as cyclic performance of Li-Ion-batteries was also discussed.
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The skin has emerge as a compelling subject for investigation owing to its accessibility and the relatively straightforward application of optical procedures to it. Diffusive reflection spectroscopy (DRS) was employed to study the influence of probe pressure on human skin. A comprehensive non-invasive study was conducted, which covers almost all the important body parts for in vivo measurements. Reflection spectra were measured for the fingertip, forearm, forehead, neck, and foot under a set of probe pressures (0-265 kPa). Importantly, each tissue type's unique composition and morphology influenced the shape, size, intensity, and position of the recorded peak, highlighting the tissue-specific responses to pressure. In addition, time-based reflection spectroscopy was also performed on the forearm under blood occlusion for 5 min to study the effect. DRS measurements were performed on volunteers of different skin tones, including dark, medium, and fair. Later, a change in the intensity of the oxyhemoglobin peak was confirmed using a green laser light of a wavelength of 532 nm. Besides the dermal studies, diffusive reflection spectroscopy was also employed to investigate the probe pressure effect on human nails. A probe pressure ranging from 0 to 385 kPa was applied for nail spectroscopy. The same trend of intensity change was observed following the previous measurements. The suggested sensing system may be crucial in applications requiring pressure sensing when the human body is subjected to varying pressures, such as exercise, weightlifting, and other sports.
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Lymphoma when arising from sites other than lymph nodes is termed extranodal lymphoma, commonly affecting the gastrointestinal tract. Primary colorectal lymphoma is a rare phenomenon among malignancies affecting the colon. We report a case of a patient with a history of Burkitt lymphoma in remission, presenting with a large cecal mass and a new diagnosis of diffuse large B-cell lymphoma treated with chemotherapy.
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Flexible photonic devices based on soft polymers enable real-time sensing of environmental conditions in various industrial applications. A myriad of fabrication techniques have been established for producing optical devices, including photo and electron-beam lithography, nano/femtosecond laser writing, and surface imprinting or embossing. However, among these techniques, surface imprinting/embossing is simple, scalable, convenient to implement, can produce nanoscale resolutions, and is cost-effective. Herein, we utilize the surface imprinting method to replicate rigid micro/nanostructures onto a commonly available PDMS substrate, enabling the transfer of rigid nanostructures into flexible forms for sensing at a nanometric scale. The sensing nanopatterned sheets were mechanically extended, and the extension was remotely monitored via optical methods. Monochromatic light (450, 532, and 650 nm) was transmitted through the imprinted sensor under various force/stress levels. The optical response was recorded on an image screen and correlated with the strain created by the applied stress levels. The optical response was obtained in diffraction pattern form from the flexible grating-based sensor and in an optical-diffusion field form from the diffuser-based sensor. The calculated Young's modulus in response to the applied stress, measured through the novel optical method, was found in a reasonable range compared to the reported range of PDMS (360-870 kPa) in the literature.
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Optical fiber (OF) sensors are critical optical devices with excellent sensing capabilities and the capacity to operate in remote and hostile environments. However, integrating functional materials and micro/nanostructures into the optical fiber systems for specific sensing applications has limitations of compatibility, readiness, poor control, robustness, and cost-effectiveness. Herein, we have demonstrated the fabrication and integration of stimuli-responsive optical fiber probe sensors using a novel, low-cost, and facile 3D printing process. Thermal stimulus-response of thermochromic pigment micro-powders was integrated with optical fibers by incorporating them into ultraviolet-sensitive transparent polymer resins and then printed via a single droplet 3D printing process. Hence, the thermally active polymer composite fibers were grown (additively manufactured) on top of the commercial optical fiber tips. Then, the thermal response was studied within the temperature range of (25-35 °C) and (25-31 °C) for unicolor and dual color pigment powders-based fiber-tip sensors, respectively. The unicolor (with color to colorless transition) and dual color (with color to color transition) powders-based sensors exhibited substantial variations in transmission and reflection spectra by reversibly increasing and decreasing temperatures. The sensitivities were calculated from the transmission spectra where average change in transmission spectra was recorded as 3.5% with every 1 °C for blue, 3% for red and 1% for orange-yellow thermochromic powders based optical fiber tip sensors. Our fabricated sensors are cost-effective, reusable, and flexible in terms of materials and process parameters. Thus, the fabrication process can potentially develop transparent and tunable thermochromic sensors for remote sensing with a much simpler manufacturing process compared to conventional and other 3D printing processes for optical fiber sensors. Moreover, this process can integrate micro/nanostructures as patterns on the optical fiber tips to increase sensitivity. The developed sensors may be employed as remote temperature sensors in biomedical and healthcare applications.
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Mycophenolate mofetil (MMOF) is a commonly used immunosuppressive prodrug in kidney transplant patients. However, it is not without side effects. The most common of these is diarrhea which inadvertently leads to colonoscopic and endoscopic evaluation when all other workup returns negative. Colonoscopies often show diffuse ulcers and colitis changes depending on the degree of diarrhea. In rare situations, MMOF-induced ischemic colitis may occur on gross endoscopy. We describe an unusual phenomenon of an adult male status post renal transplant with histopathologically diagnosed MMOF-induced colitis who developed gross endoscopic findings concerning ischemic colitis. Our case highlights the importance of recognizing that MMOF-induced colonic changes can rarely mimic ischemic colitis. With this in mind, we aim for gastroenterologists to better understand the varying endoscopic colonic findings of this immunosuppressive drug.
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OBJECTIVE: To determine the factors affecting the frequency and severity of oral mucositis are following hematopoietic stem cell transplantation. STUDY DESIGN: Descriptive study. Place and Duration of the Study: Armed Forces Bone Marrow Transplant Centre Rawalpindi, from September 2020 to February 2022. METHODOLOGY: Patients who underwent allogenic stem cell transplantation were enrolled. Patients were analysed based on history and examination for oral mucositis (OM) as per the WHO mucositis scale, from the start of conditioning chemotherapy till discharge, total duration of mucositis and type of medication were noted. Its association with risk factors like age, gender, conditioning chemotherapy, methotrexate (MTX) for GVHD prophylaxis, and prior history of irradiation was determined. RESULTS: Mean age of the 72 transplant recipients was 21.9 ± 14 years, with 48 males and 24 females. The common underlying diseases were beta-thalassemia major (30.6%, n=22), acute lymphoblastic leukaemia (n=15, 20.8%), aplastic anaemia (n=10, 13.9%), and multiple myeloma (n=8, 11.1%). The frequency of mucositis in those aged under 15 years was 79.3% (n=23) and in those older than 15 years was 74.4% (n=32). Frequency of mucositis was statistically significant in patients who received myeloablative conditioning regimen (85% vs. 20%, p <0.01), and who had prophylactic. MTX (91% vs. 48%, p<0.01) and who had prior craniospinal (CSI) radiation (100% vs. 70.2%, p=0.01). There was no statistical significance between stem cell dose (CD34/TNC) and mucositis. Severity of mucositis was significantly greater in Allogenic vs. auto HSCT (p=0.04). All the patients with mucositis required analgesics for pain management. CONCLUSION: Oral mucositis is a common but potentially debilitating complication of stem cell transplant, requiring opioid analgesia in a significant number of cases. Myeloablative conditioning, prophylactic MTX, and prior CSI are significantly associated with mucositis in transplant patients. KEY WORDS: Hematopoietic stem cell transplantation (HSCT), Oral Mucositis, Myeloablative conditioning, Methotrexate, Analgesia.
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Transplante de Células-Tronco Hematopoéticas , Mucosite , Mieloma Múltiplo , Estomatite , Masculino , Feminino , Humanos , Idoso , Criança , Adolescente , Adulto Jovem , Adulto , Mucosite/induzido quimicamente , Metotrexato/uso terapêutico , Estomatite/prevenção & controle , Estomatite/induzido quimicamente , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Condicionamento Pré-Transplante/efeitos adversosRESUMO
Zinc (Zn) is an indispensable element for proper plant growth. A sizeable proportion of the inorganic Zn that is added to soil undergoes a transformation into an insoluble form. Zinc-solubilizing bacteria (ZSB) have the potential to transform the insoluble Zn into plant-accessible forms and are thus promising alternatives for Zn supplementation. The current research was aimed at investigating the Zn solubilization potential of indigenous bacterial strains and to evaluate their impact on wheat growth and Zn biofortification. A number of experiments were conducted at the National Agriculture Research Center (NARC), Islamabad, during 2020-21. A total of 69 strains were assessed for their Zn-solubilizing ability against two insoluble Zn sources (ZnO and ZnCO3) using plate assay techniques. During the qualitative assay, the solubilization index and solubilization efficiency were measured. The qualitatively selected Zn-solubilizing bacterial strains were further tested quantitatively using broth culture for Zn and phosphorus (P) solubility. Tricalcium phosphate was used as insoluble source of P. The results showed that broth culture pH was negatively correlated with Zn solubilization, i.e., ZnO (r2 = 0.88) and ZnCO3 (r2 = 0.96). Ten novel promising strains, i.e., Pantoea sp. NCCP-525, Klebsiella sp. NCCP-607, Brevibacterium sp. NCCP-622, Klebsiella sp. NCCP-623, Acinetobacter sp. NCCP-644, Alcaligenes sp. NCCP-650, Citrobacter sp. NCCP-668, Exiguobacterium sp. NCCP-673, Raoultella sp. NCCP-675, and Acinetobacter sp. NCCP-680, were selected from the ecology of Pakistan for further experimentation on wheat crop based on plant growth-promoting rhizobacteria (PGPR) traits, i.e., solubilization of Zn and P in addition to being positive for nifH and acdS genes. Before evaluating the bacterial strains for plant growth potential, a control experiment was also conducted to determine the highest critical Zn level from ZnO to wheat growth using different Zn levels (0.1, 0.05, 0.01, 0.005, and 0.001% Zn) against two wheat varieties (Wadaan-17 and Zincol-16) in sand culture under glasshouse conditions. Zinc-free Hoagland nutrients solution was used to irrigate the wheat plants. As a result, 50 mg kg-1 of Zn from ZnO was identified as the highest critical level for wheat growth. Using the critical level (50 mg kg-1 of Zn), the selected ZSB strains were inoculated alone and in consortium to the seed of wheat, with and without the use of ZnO, in sterilized sand culture. The ZSB inoculation in consortium without ZnO resulted in improved shoot length (14%), shoot fresh weight (34%), and shoot dry weight (37%); with ZnO root length (116%), it saw root fresh weight (435%), root dry weight (435%), and Zn content in the shoot (1177%) as compared to the control. Wadaan-17 performed better on growth attributes, while Zincol-16 had 5% more shoot Zn concentration. The present study concluded that the selected bacterial strains show the potential to act as ZSB and are highly efficient bio-inoculants to combat Zn deficiency, and the inoculation of these strains in consortium performed better in terms of growth and Zn solubility for wheat as compared to individual inoculation. The study further concluded that 50 mg kg-1 Zn from ZnO had no negative impact on wheat growth; however, higher concentrations hampered wheat growth.
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As therapeutic agents that allow for minimally invasive administration, injectable biomaterials stand out as effective tools with tunable properties. Furthermore, hydrogels with responsive features present potential platforms for delivering therapeutics to desired sites in the body. Herein, temperature-responsive hydrogel scaffolds with embedded targeted nanoparticles were utilized to achieve controlled drug delivery via local drug administration. Poly(N-isopropylacrylamide) (pNIPAM) hydrogels, prepared with an ethylene-glycol-based cross-linker, demonstrated thermo-sensitive gelation ability upon injection into environments at body temperature. This hydrogel network was engineered to provide a slow and controlled drug release profile by being incorporated with curcumin-loaded nanoparticles bearing high encapsulation efficiency. A core (alginate)-shell (chitosan) nanoparticle design was preferred to ensure the stability of the drug molecules encapsulated in the core and to provide slower drug release. Nanoparticle-embedded hydrogels were shown to release curcumin at least four times slower compared to the free nanoparticle itself and to possess high water uptake capacity and more mechanically stable viscoelastic behavior. Moreover, this therapy has the potential to specifically address tumor tissues over-expressing folate receptors like ovaries, as the nanoparticles target the receptors by folic acid conjugation to the periphery. Together with its temperature-driven injectability, it can be concluded that this hydrogel scaffold with drug-loaded and embedded folate-targeting nanoparticles would provide effective therapy for tumor tissues accessible via minimally invasive routes and be beneficial for post-operative drug administration after tumor resection.
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Whistleblowers have significantly shaped the state of contemporary society; in this context, this research sheds light on a persistently neglected research area: what are the key determinants of whistleblowing within government agencies? Taking a unique methodological approach, we combine evidence from two pieces of fieldwork, conducted using both primary and secondary data from the US and Indonesia. In Study 1, we use a large-scale survey conducted by the US Merit Systems Protection Board (MSPB). Additional tests are conducted in Study 1, making comparisons between those who have and those who do not have whistleblowing experience. In Study 2, we replicate the survey conducted by the MSPB, using empirical data collected in Indonesia. We find a mixture of corroboration of previous results and unexpected findings between the two samples (US and Indonesia). The most relevant result is that perceived organizational protection has a significant positive effect on whistleblowing intention in the US sample, but a similar result was not found in the Indonesian sample. We argue that this difference is potentially due to the weakness of whistleblowing protection in Indonesia, which opens avenues for further understanding the role of societal cultures in protecting whistleblowers around the globe. Supplementary Information: The online version contains supplementary material available at 10.1007/s10551-022-05089-y.
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Mismatch repair/microsatellite instability (MMR/MSI) status in colorectal cancer (CRC) has become fundamental as a diagnostic, prognostic, and predictive factor. MMR immunohistochemistry (IHC) is considered a simple and reliable approach; however, its effectiveness depends on pre-analytic factors. Aim of this study was to investigate the impact of different fixation times/protocols on MMR protein IHC quality. Left over tissue from surgically resected CRC samples (cold ischemia time < 30 min) where fixed as follows: standard formalin fixation (24-48 h); hypo-fixation (<20 h); hyper-fixation (>90 h); cold (4°C) fixation (24-48 h); standard fixation for small sample size (0.5×0.5 cm). Samples for each group were collected from 30 resected CRC and the following parameters were evaluated on 600 immunohistochemical stains: intensity of expression; patchiness of staining; presence of central artefact. Forty-six immunoreactions were inadequate (score 0 intensity), the majority regarding MLH1 or PMS2 in the hypo-fixation group (47.8%), followed by the hyper-fixation group (28.1%); cold formalin fixation showed the least inadequate cases. Patchiness and central artefact were more frequent in hypo-fixation and standard fixation group compared to the others. MLH1 (closely followed by PMS2) performed worse with regard to immunostaining intensity (p=0.0002) in the standard and in the hypo-fixation group (p< 0.00001). Using a small sample size improved patchiness/central artefacts. This is the first study specifically created to evaluate the impact of fixation on MMR protein IHC, showing that both formalin hypo- and hyper-fixation can cause problems; 24-h formalin fixation as well as cold (4°C) formalin fixation are recommended for successful IHC MMR evaluation.