Expression of the Arabidopsis Mg-chelatase H subunit alleviates iron deficiency-induced stress in transgenic rice.

The most common symptom of iron (Fe) deficiency in plants is leaf chlorosis caused by impairment of chlorophyll biosynthesis. Magnesium (Mg)-chelatase H subunit (CHLH) is a key component in both chlorophyll biosynthesis and plastid signaling, but its role in Fe deficiency is poorly understood. Heterologous expression of the Arabidopsis thaliana Mg-chelatase H subunit gene (AtCHLH) increased Mg-chelatase activity by up to 6-fold and abundance of its product, Mg-protoporphyrin IX (Mg-Proto IX), by 60-75% in transgenic rice (Oryza sativa) seedlings compared to wild-type (WT) controls. Noticeably, the transgenic seedlings showed alleviation of Fe deficiency symptoms, as evidenced by their less pronounced leaf chlorosis and lower declines in shoot growth, chlorophyll contents, and photosynthetic efficiency, as indicated by F v/F m and electron transport rate, compared to those in WT seedlings under Fe deficiency. Porphyrin metabolism was differentially regulated by Fe deficiency between WT and transgenic seedlings, particularly with a higher level of Mg-Proto IX in transgenic lines, showing that overexpression of AtCHLH reprograms porphyrin metabolism in transgenic rice. Leaves of Fe-deficient transgenic seedlings exhibited greater upregulation of deoxymugineic acid biosynthesis-related genes (i.e., NAS, NAS2, and NAAT1), YSL2 transporter gene, and Fe-related transcription factor genes IRO2 and IDEF2 than those of WT, which may also partly contribute to alleviating Fe deficiency. Although AtCHLH was postulated to act as a receptor for abscisic acid (ABA), exogenous ABA did not alter the phenotypes of Fe-deficient WT or transgenic seedlings. Our study demonstrates that modulation of porphyrin biosynthesis through expression of AtCHLH in transgenic rice alleviates Fe deficiency-induced stress, suggesting a possible role for CHLH in Fe deficiency responses.

An Intersectional Approach to Hepatitis B.

Hepatitis B is a chronic condition, primarily associated with hepatitis B viral infection in early life. The failure of prevention and appropriate management can lead to subsequent liver cirrhosis and cancer. Hepatitis B most commonly affects people born in Asia and Sub-Saharan Africa and their global diasporas. The physical, psychological, and social impacts of hepatitis B are strongly influenced by sex and gender. Inequities in access to timely, sensitive diagnosis and effective management arise from interactions between structural inequalities related to race, ethnicity, Indigenous/settler status, class, and geography. The biomedical response to hepatitis B has led to advances in prevention, diagnosis, and treatment, but many affected communities have explanatory health belief models that differ from that of biomedicine. We argue that an intersectional approach, led by affected people and communities, can integrate biomedicine with the lived experience and social context that give purpose to and shape all personal, communal, clinical, and public health responses to hepatitis B. This approach has the potential to enable a consciously equitable, effective response to the biopsychosocial complexities of hepatitis B, improve the health and wellbeing of people living with hepatitis B, and reduce hepatitis B-associated mortality.

Pulmonary hypertension in metastatic breast cancer: a case of pulmonary tumour thrombotic microangiopathy.

Pulmonary tumour thrombotic microangiopathy (PTTM) and pulmonary tumour emboli (PTE) are distinct but related complications of malignancy. The incidence of each is exceedingly rare, unfortunately often being diagnosed postmortem. Patients with PTTM and PTE typically present with dyspnoea associated with a rapid onset of hypoxia due to pulmonary hypertension (PH), and respiratory failure that is almost certain to be fatal. The prognosis is grim due to the rapidity of the clinical decline and difficulty in establishing an ante-mortem diagnosis. We present a case of new-onset severe PH in a young woman with a recently discovered breast mass. She presented with shortness of breath and experienced rapid deterioration of her cardiopulmonary status which we attributed to PTTM. With early initiation of chemotherapy, systemic steroids and sildenafil, the patient dramatically improved. Case reports have identified early use of steroids, phosphodiesterase inhibitors and other alternative therapies as providing possible benefit in PTTM.

Bone Marrow Mononuclear Cells Transplantation in Treatment of Established Bronchopulmonary Dysplasia: A Case Report.

BACKGROUND Bronchopulmonary dysplasia (BDP) is an incurable disease. This study reports the successful treatment of a 30-week-old neonate with established bronchopulmonary dysplasia by bone marrow mononuclear cells (BM MNCs) transplantation. CASE REPORT The preterm infant with BPD requiring continuous oxygen administration for 4 months post-delivery underwent BM MNCs. Bone marrow was obtained from the patient's iliac crests and mononuclear cells were isolated by density gradient centrifugation method. BM MNCs were delivered via endotracheal and intravenous routes. After BM MNCs transplantation, remarkable improvements were observed in oxygen saturation and lung CT as the infant was gradually weaned off oxygen supply. CONCLUSIONS BM MNCs transplantation offers promising treatment of BPD.

Perioperative Pain Control in the Ambulatory Setting.

Across the USA and various parts of the world, ambulatory surgery centers have transitioned to accepting patients with advanced ASA statuses, leading to a larger volume and higher complexity of surgeries performed, while still urging for same-day patient discharges. Inadequate postoperative pain management and opioid analgesia side effects, such as sedation, respiratory depression, and postoperative nausea and vomiting, are the most common complications and most common reasons for readmission after ambulatory surgery. The trend to limiting these complications and achieve a more rapid patient discharge currently emphasizes a multifactorial, balanced analgesia strategy. This article reviews the multimodal approach by detailing the important aspects of specific regional nerve blocks, nerve blockade with catheter techniques, acetaminophen, non-selective NSAIDs, Cox-2 inhibitors, membrane stabilizers, and corticosteroids. Pain management in the ambulatory surgery patient will thus be optimized with a thorough preoperative evaluation, recognizing intraoperative events, and implementing multiple analgesic modalities.

Integration of structure-activity relationship and artificial intelligence systems to improve in silico prediction of ames test mutagenicity.

The Ames mutagenicity test in Salmonella typhimurium is a bacterial short-term in vitro assay aimed at detecting the mutagenicity caused by chemicals. Mutagenicity is considered as an early alert for carcinogenicity. After a number of decades, several (Q)SAR studies on this endpoint yielded enough evidence to make feasible the construction of reliable computational models for prediction of mutagenicity from the molecular structure of chemicals. In this study, we propose a combination of a fragment-based SAR model and an inductive database. The hybrid system was developed using a collection of 4337 chemicals (2401 mutagens and 1936 nonmutagens) and tested using 753 independent compounds (437 mutagens and 316 nonmutagens). The overall error of this system on the external test set compounds is 15% (sensitivity = 15%, specificity = 15%), which is quantitatively similar to the experimental error of Ames test data (average interlaboratory reproducibility determined by the National Toxicology Program). Moreover, each single prediction is provided with a specific confidence level. The results obtained give confidence that this system can be applied to support early and rapid evaluation of the level of mutagenicity concern.

An architecture for computer-aided detection and radiologic measurement of lung nodules in clinical trials.

Computer tomography (CT) imaging plays an important role in cancer detection and quantitative assessment in clinical trials. High-resolution imaging studies on large cohorts of patients generate vast data sets, which are infeasible to analyze through manual interpretation. In this article we describe a comprehensive architecture for computer-aided detection (CAD) and surveillance on lung nodules in CT images. Central to this architecture are the analytic components: an automated nodule detection system, nodule tracking capabilities and volume measurement, which are integrated within a data management system that includes mechanisms for receiving and archiving images, a database for storing quantitative nodule measurements and visualization, and reporting tools. We describe two studies to evaluate CAD technology within this architecture, and the potential application in large clinical trials. The first study involves performance assessment of an automated nodule detection system and its ability to increase radiologist sensitivity when used to provide a second opinion. The second study investigates nodule volume measurements on CT made using a semi-automated technique and shows that volumetric analysis yields significantly different tumor response classifications than a 2D diameter approach. These studies demonstrate the potential of automated CAD tools to assist in quantitative image analysis for clinical trials.

Estradiol reduces activity of the blood-brain barrier Na-K-Cl cotransporter and decreases edema formation in permanent middle cerebral artery occlusion.

Estrogen has been shown to protect against stroke-induced brain damage, yet the mechanism is unknown. During the early hours of stroke, cerebral edema forms as increased transport of Na and Cl from blood into brain occurs across an intact blood-brain barrier (BBB). We showed previously that a luminal BBB Na-K-Cl cotransporter is stimulated by hypoxia and arginine vasopressin (AVP), factors present during cerebral ischemia, and that inhibition of the cotransporter by intravenous bumetanide greatly reduces edema in rats subjected to permanent middle cerebral artery occlusion (MCAO). The present study was conducted to determine whether estrogen protects in stroke at least in part by reducing activity of the BBB cotransporter, thereby decreasing edema formation. Ovariectomized rats were subjected to 210 mins of permanent MCAO after 7-day or 30-min pretreatment with 17beta-estradiol and then brain swelling and 2,3,5-triphenyltetrazolium chloride staining were assessed as measures of brain edema and lesion volume, respectively. Diffusion-weighed imaging was used to monitor permanent MCAO-induced decreases in apparent diffusion coefficient (ADC) values, an index of changes in brain water distribution and mobility. Na-K-Cl cotransporter activity of cerebral microvascular endothelial cells (CMECs) was assessed as bumetanide-sensitive K influx and cotransporter abundance by Western blot analysis after estradiol treatment. Estradiol significantly decreased brain swelling and lesion volume and attenuated the decrease in ADC values during permanent MCAO. Estradiol also abolished CMEC cotransporter stimulation by chemical hypoxia or AVP and decreased cotransporter abundance. These findings support the hypothesis that estrogen attenuates stimulation of BBB Na-K-Cl cotransporter activity, reducing edema formation during stroke.

Cloning and expression of NAD+-dependent L-arabinitol 4-dehydrogenase gene (ladA) of Aspergillus oryzae.

A gene of Aspergillus oryzae, ladA, which encodes L-arabinitol 4-dehydrogenase (EC 1.1.1.12), and its cDNA were cloned in Escherichia coli. The gene consisted of a 1209-bp coding region, interrupted by a 59-bp intron, which encoded a 382-amino-acid polypeptide (40,812 Da). The protein showed 67% identity to a well-studied L-arabinitol 4-dehydrogenase (Lad1) of Hypocrea jecorina. The cell-free extract of E. coli, which expressed ladA cDNA, showed L-arabinitol dehydrogenase activity with NAD+. It was also reactive for ribitol and xylitol.

Comparison of treatment response classifications between unidimensional, bidimensional, and volumetric measurements of metastatic lung lesions on chest computed tomography.

RATIONALE AND OBJECTIVES: To study the agreement in treatment response classifications between unidimensional (1D), bidimensional (2D), and volumetric (3D) methods of measuring metastatic lung nodules on chest computed tomography (CT). MATERIALS AND METHODS: Chest CT scans of 15 patients undergoing treatment for metastatic colorectal, renal cell, or breast carcinoma to the lungs were analyzed. CT images were acquired with 3 mm collimation and contiguous reconstruction. Two or three lung lesions were selected for each patient. Lesions were analyzed at baseline and two follow-up intervals of 1-4 months. 1D and 2D measurements were made with electronic calipers, while nodule volume was measured using a semiautomated segmentation system. Following the World Health Organization and RECIST (Response Evaluation Criteria in Solid Tumors) criteria, patients were categorized into four treatment response classifications. Volumetric criteria were used to classify response based on 3D measurements. RESULTS: Thirty-two lesions from 15 patients were analyzed. Because each patient had a baseline and two follow-up scans, this yielded 30 response classifications for each measurement technique. The 1D, 2D, and 3D measurements were concordant in 21 of 30 classifications. The 1D and 3D measurements were concordant in 29 of 30 classifications, while the 2D and 3D measurements were concordant in 23 of 30 classifications. Level of agreement among the three methods was measured using a kappa statistic (K). For 1D compared with 3D, K = 0.739 +/- 0.345 (visits 1, 2) and 0.273 +/- 0.323 (visits 2, 3). For 2D compared with 3D, K = 0.655 +/- 0.325 (visits 1, 2) and 0.200 +/- 0.208 (visits 2, 3). Agreement among the methods for round and ovoid nodules was also fair to poor. CONCLUSION: The three methods of tumor measurement show fair to poor agreement in treatment response classification. These findings have negative implications for the accuracy in which patients are classified under the World Health Organization or RECIST criteria and managed under cancer treatment protocols.