N-acetylgalatosamine-Mediated Regulation of the aga Operon by AgaR in Streptococcus pneumoniae

Here, we analyze the transcriptomic response of Streptococcus pneumoniae D39 to N-acetylgalactosamine (NAGa). Transcriptome comparison of S. pneumoniae D39 grown in NAGaM17 (0.5% NAGa + M17) to that grown in GM17 (0.5% Glucose + M17) revealed the elevated expression of various carbon metabolic genes/operons, including a PTS operon (denoted here as the aga operon), which is putatively involved in NAGa transport and utilization, in the presence of NAGa. We further studied the role of a GntR-family transcriptional regulator (denoted here as AgaR) in the regulation of aga operon. Our transcriptome and RT-PCR data suggest the role of AgaR as a transcriptional repressor of the aga operon. We predicted a 20-bp operator site of AagR (5'-ATAATTAATATAACAACAAA-3') in the promoter region of the aga operon (PbgaC), which was further verified by mutating the AgaR operator site in the respective promoter. The role of CcpA in the additional regulation of the aga operon was elucidated by further transcriptome analyses and confirmed by quantitative RT-PCR.</p

Augmentation of Fatigue and Tensile Strength of AA-6061 Processed through Equal Channel Angular Pressing

ECAP (Equal Channel Angular Pressing) is a technique used to enhance the strength of material by grain refinement. In this research, an aerospace grade aluminum alloy-6061 is investigated. The specimens were pressed through ECAP die channels, intersecting each other at an angle of 90oC where a shear plane of 45oC was developed, that results grains refinement. Fatigue strengths and CGR (Crack Growth Rate) for the stress ratio R 0.7 and 0.1 are found and compared with the as-received material.It was observed that the CGR is slower at stress ratio R=0.1, as compared to stress ration R=0.7. An electric furnace was embedded with ECAP die to regulate the material flow through this die. The temperature of the die was maintained at 450oC during ECAP pressing and the specimens were also preheated at this temperature using another furnace. The ECAP die consistsof two channels intersecting at 90o provided with safe inner and outer corner radius to avoid scaling.The microstructural observations revealed that the deformation was perfectly plastic. The ECAPed and as-received materials were also characterized by tensile tests, micro-hardness tests, and 3-point bend fatigue tests

The dosimetric effects of limited elective nodal irradiation in volumetric modulated arc therapy treatment planning for locally advanced non-small cell lung cancer

Objective—Contemporary radiotherapy guidelines for locally advanced non-small cell lung carcinoma (LA-NSCLC) recommend omitting elective nodal irradiation, despite the fact that evidence supporting this came primarily from older reports assessing comprehensive nodal coverage using 3D conformal techniques. Herein, we evaluated the dosimetric implications of the addition of limited elective nodal irradiation (LENI) to standard involved field irradiation (IFI) using volumetric modulated arc therapy (VMAT) planning. Method—Target volumes and organs-at-risk (OARs) were delineated on CT simulation images of 20 patients with LA-NSCLC. Two VMAT plans (IFI and LENI) were generated for each patient. Involved sites were treated to 60 Gy in 30 fractions for both IFI and LENI plans. Adjacent uninvolved nodal regions, considered high risk based on the primary tumor site and extent of nodal involvement, were treated to 51 Gy in 30 fractions in LENI plans using a simultaneous integrated boost approach. Results—All planning objectives for PTVs and OARs were achieved for both IFI and LENI plans. LENI resulted in significantly higher esophagus Dmean (15.3 vs. 22.5 Gy, p \u3c 0.01), spinal cord Dmax (34.9 vs. 42.4 Gy, p = 0.02) and lung Dmean (13.5 vs. 15.9 Gy, p = 0.02), V20 (23.0 vs. 27.9%, p = 0.03), and V5 (52.6 vs. 59.4%, p = 0.02). No differences were observed in heart parameters. On average, only 32.2% of the high-risk nodal volume received an incidental dose of 51 Gy when untargeted in IFI plans. Conclusion—The addition of LENI to VMAT plans for LA-NSCLC is feasible, with only modestly increased doses to OARs and marginal expected increase in associated toxicity

Quantifying soil moisture impacts on light use efficiency across biomes.

Terrestrial primary productivity and carbon cycle impacts of droughts are commonly quantified using vapour pressure deficit (VPD) data and remotely sensed greenness, without accounting for soil moisture. However, soil moisture limitation is known to strongly affect plant physiology. Here, we investigate light use efficiency, the ratio of gross primary productivity (GPP) to absorbed light. We derive its fractional reduction due to soil moisture (fLUE), separated from VPD and greenness changes, using artificial neural networks trained on eddy covariance data, multiple soil moisture datasets and remotely sensed greenness. This reveals substantial impacts of soil moisture alone that reduce GPP by up to 40% at sites located in sub-humid, semi-arid or arid regions. For sites in relatively moist climates, we find, paradoxically, a muted fLUE response to drying soil, but reduced fLUE under wet conditions. fLUE identifies substantial drought impacts that are not captured when relying solely on VPD and greenness changes and, when seasonally recurring, are missed by traditional, anomaly-based drought indices. Counter to common assumptions, fLUE reductions are largest in drought-deciduous vegetation, including grasslands. Our results highlight the necessity to account for soil moisture limitation in terrestrial primary productivity data products, especially for drought-related assessments

Multiorgan MRI findings after hospitalisation with COVID-19 in the UK (C-MORE): a prospective, multicentre, observational cohort study

Introduction: The multiorgan impact of moderate to severe coronavirus infections in the post-acute phase is still poorly understood. We aimed to evaluate the excess burden of multiorgan abnormalities after hospitalisation with COVID-19, evaluate their determinants, and explore associations with patient-related outcome measures. Methods: In a prospective, UK-wide, multicentre MRI follow-up study (C-MORE), adults (aged ≥18 years) discharged from hospital following COVID-19 who were included in Tier 2 of the Post-hospitalisation COVID-19 study (PHOSP-COVID) and contemporary controls with no evidence of previous COVID-19 (SARS-CoV-2 nucleocapsid antibody negative) underwent multiorgan MRI (lungs, heart, brain, liver, and kidneys) with quantitative and qualitative assessment of images and clinical adjudication when relevant. Individuals with end-stage renal failure or contraindications to MRI were excluded. Participants also underwent detailed recording of symptoms, and physiological and biochemical tests. The primary outcome was the excess burden of multiorgan abnormalities (two or more organs) relative to controls, with further adjustments for potential confounders. The C-MORE study is ongoing and is registered with ClinicalTrials.gov, NCT04510025. Findings: Of 2710 participants in Tier 2 of PHOSP-COVID, 531 were recruited across 13 UK-wide C-MORE sites. After exclusions, 259 C-MORE patients (mean age 57 years [SD 12]; 158 [61%] male and 101 [39%] female) who were discharged from hospital with PCR-confirmed or clinically diagnosed COVID-19 between March 1, 2020, and Nov 1, 2021, and 52 non-COVID-19 controls from the community (mean age 49 years [SD 14]; 30 [58%] male and 22 [42%] female) were included in the analysis. Patients were assessed at a median of 5·0 months (IQR 4·2–6·3) after hospital discharge. Compared with non-COVID-19 controls, patients were older, living with more obesity, and had more comorbidities. Multiorgan abnormalities on MRI were more frequent in patients than in controls (157 [61%] of 259 vs 14 [27%] of 52; p&lt;0·0001) and independently associated with COVID-19 status (odds ratio [OR] 2·9 [95% CI 1·5–5·8]; padjusted=0·0023) after adjusting for relevant confounders. Compared with controls, patients were more likely to have MRI evidence of lung abnormalities (p=0·0001; parenchymal abnormalities), brain abnormalities (p&lt;0·0001; more white matter hyperintensities and regional brain volume reduction), and kidney abnormalities (p=0·014; lower medullary T1 and loss of corticomedullary differentiation), whereas cardiac and liver MRI abnormalities were similar between patients and controls. Patients with multiorgan abnormalities were older (difference in mean age 7 years [95% CI 4–10]; mean age of 59·8 years [SD 11·7] with multiorgan abnormalities vs mean age of 52·8 years [11·9] without multiorgan abnormalities; p&lt;0·0001), more likely to have three or more comorbidities (OR 2·47 [1·32–4·82]; padjusted=0·0059), and more likely to have a more severe acute infection (acute CRP &gt;5mg/L, OR 3·55 [1·23–11·88]; padjusted=0·025) than those without multiorgan abnormalities. Presence of lung MRI abnormalities was associated with a two-fold higher risk of chest tightness, and multiorgan MRI abnormalities were associated with severe and very severe persistent physical and mental health impairment (PHOSP-COVID symptom clusters) after hospitalisation. Interpretation: After hospitalisation for COVID-19, people are at risk of multiorgan abnormalities in the medium term. Our findings emphasise the need for proactive multidisciplinary care pathways, with the potential for imaging to guide surveillance frequency and therapeutic stratification

Sialic acid-mediated gene expression in Streptococcus pneumoniae and the role of NanR as a transcriptional activator of the nan gene cluster

In this study, we investigated the transcriptomic response of Streptococcus pneumoniae D39 to sialic acid (N-acetylneuraminic acid: Neu5Ac). Transcriptome comparison of the D39 wild-type grown in M17 medium with and without sialic acid revealed the elevated expression of various genes and operons including the nan gene cluster (nan operon-I and nanA gene). Our microarray analysis and promoter-lacZ fusion studies showed that the transcriptional regulator NanR, acts as a transcriptional activator of nan operon-I and the nanA gene in the presence of sialic acid. The putative regulatory site of NanR in the promoter region of nan operon-I is predicted and confirmed by promoter truncation experiments. Furthermore, the role of CcpA in the regulation of the nan gene cluster is demonstrated through microarray analysis and promoter-lacZ fusion studies, suggesting that in the presence of sialic acid and glucose, CcpA represses the expression of nan operon-I while the expression of the nanA gene is CcpA-independent

Epidemiological Insights and Statistical Analysis of a Recent Conjunctivitis Outbreak in Lahore, Pakistan

This study presents a comprehensive epidemiological analysis of a recent outbreak of conjunctivitis, known as pink eye disease, in Lahore, Pakistan. Conjunctivitis is a highly contagious eye infection that poses a significant public health concern, particularly in social environments. The research focuses on understanding the prevalence and influencing factors of this ailment through a statistical analysis of patient data. The gender distribution among patients revealed a slightly higher prevalence among males (52.5%) as compared to females (47.5%). Young adults (age 18-25) comprised the highest affected group (89%), emphasizing the higher infection\u27s prevalence among this demographic. Symptom analysis highlights moderate to severe manifestations as predominant, significantly impacting patients\u27 daily routines. Males exhibit a higher severity, potentially associated with increased social engagement compared to females. Notably, the infection commonly affects both eyes (86%), and individuals with a history of prior eye infections demonstrate a reduced likelihood of contracting conjunctivitis (11%). The onset of symptoms is typically sudden (85%), with a gradual presentation in some cases (15%). Despite the contagious nature of the infection, its spread to family members’ remains relatively limited (36.8%). Remarkably, although symptoms are severe, the duration of the infection is brief, with most patients recovering within 2-5 days, even without medical consultation. Moreover, the spatial distribution showed that redness and itchiness were very severe in location 1(latitude 31.4972, and longitude 74.2735) and severe in location 4 (latitude 31.508, and longitude 74.327). In conclusion, this study is the first to report on the rapid yet severe nature of a conjunctivitis outbreak in Lahore. Key trends, including gender disparities, previous eye infection history, sudden onset of symptoms, and limited familial transmission, have emerged. Understanding these dynamics is crucial for implementing targeted preventive measures and developing effective management strategies for this contagious eye infection. The findings contribute valuable epidemiological insights that can guide public health interventions in similar scenarios

Epidemiological Insights and Statistical Analysis of a Recent Conjunctivitis Outbreak in Lahore, Pakistan

This study presents a comprehensive epidemiological analysis of a recent outbreak of conjunctivitis, known as pink eye disease, in Lahore, Pakistan. Conjunctivitis is a highly contagious eye infection that poses a significant public health concern, particularly in social environments. The research focuses on understanding the prevalence and influencing factors of this ailment through a statistical analysis of patient data. The gender distribution among patients revealed a slightly higher prevalence among males (52.5%) as compared to females (47.5%). Young adults (age 18-25) comprised the highest affected group (89%), emphasizing the higher infection\u27s prevalence among this demographic. Symptom analysis highlights moderate to severe manifestations as predominant, significantly impacting patients\u27 daily routines. Males exhibit a higher severity, potentially associated with increased social engagement compared to females. Notably, the infection commonly affects both eyes (86%), and individuals with a history of prior eye infections demonstrate a reduced likelihood of contracting conjunctivitis (11%). The onset of symptoms is typically sudden (85%), with a gradual presentation in some cases (15%). Despite the contagious nature of the infection, its spread to family members’ remains relatively limited (36.8%). Remarkably, although symptoms are severe, the duration of the infection is brief, with most patients recovering within 2-5 days, even without medical consultation. Moreover, the spatial distribution showed that redness and itchiness were very severe in location 1(latitude 31.4972, and longitude 74.2735) and severe in location 4 (latitude 31.508, and longitude 74.327). In conclusion, this study is the first to report on the rapid yet severe nature of a conjunctivitis outbreak in Lahore. Key trends, including gender disparities, previous eye infection history, sudden onset of symptoms, and limited familial transmission, have emerged. Understanding these dynamics is crucial for implementing targeted preventive measures and developing effective management strategies for this contagious eye infection. The findings contribute valuable epidemiological insights that can guide public health interventions in similar scenarios

Risk factors for massive blood transfusion in cytoreductive surgery : a multivariate analysis of 243 procedures

Background: Cytoreductive surgery (CRS) combined with perioperative intraperitoneal chemotherapy (PIC) has demonstrated improved survival in selected patients with peritoneal carcinomatosis (PC). This treatment modality is associated with high blood loss and often requires massive allogenic red blood cell transfusion (MABT). Our study is the first of its kind to evaluate the risk factors for intraoperative MABT in peritonectomy procedures. Methods: Two hundred and forty-three consecutive CRS and PIC procedures were evaluated. The associations between 17 preoperative and intraoperative risk factors and intraoperative MABT (≥6 units) were assessed by univariate and multivariate analysis. Results: One hundred and eighty-six (77%) procedures required intraoperative transfusion of packed red blood cells. Ninety-one procedures required MABT (37%). Multivariate analysis showed six significant risk factors for intraoperative MABT: operative length > 9 h (p < 0.001), preoperative hemoglobin < 125 g/l (p < 0.001), operation date prior to 2004 (p = 0.002), peritoneal cancer index ≥ 16 (p = 0.006), preoperative international normalized ratio (INR) ≥ 1.2 (p = 0.008), and number of peritonectomy procedures ≥ 4 (p = 0.021). Statistical analysis also revealed that MABT was associated with increased intensive care unit (ICU) (p < 0.001), high-dependency unit (HDU) (p = 0.020), and total hospital stay (p < 0.001) and with severe morbidity (p < 0.001). Conclusions: Patients with preoperative anemia, impaired coagulation profile or extensive tumor burden are at high risk of MABT. Appropriate blood conservation strategies should be adopted in these patients on the basis of their risk factors.9 page(s