More salt, please: global patterns, responses and impacts of foliar sodium in grasslands.

Sodium is unique among abundant elemental nutrients, because most plant species do not require it for growth or development, whereas animals physiologically require sodium. Foliar sodium influences consumption rates by animals and can structure herbivores across landscapes. We quantified foliar sodium in 201 locally abundant, herbaceous species representing 32 families and, at 26 sites on four continents, experimentally manipulated vertebrate herbivores and elemental nutrients to determine their effect on foliar sodium. Foliar sodium varied taxonomically and geographically, spanning five orders of magnitude. Site-level foliar sodium increased most strongly with site aridity and soil sodium; nutrient addition weakened the relationship between aridity and mean foliar sodium. Within sites, high sodium plants declined in abundance with fertilisation, whereas low sodium plants increased. Herbivory provided an explanation: herbivores selectively reduced high nutrient, high sodium plants. Thus, interactions among climate, nutrients and the resulting nutritional value for herbivores determine foliar sodium biogeography in herbaceous-dominated systems.

Trait similarity patterns within grass and grasshopper communities: multitrophic community assembly at work.

Trait-based community assembly theory suggests that trait variation among co-occurring species is shaped by two main processes: abiotic filtering, important in stressful environments and promoting similarity, and competition, more important in productive environments and promoting dissimilarity. Previous studies have indeed found trait similarity to decline along productivity gradients. However, these studies have always been done on single trophic levels. Here, we investigated how interactions between trophic levels affect trait similarity patterns along environmental gradients. We propose three hypotheses for the main drivers of trait similarity patterns of plants and herbivores along environmental gradients: (1) environmental control of both, (2) bottom-up control of herbivore trait variation, and (3) top-down control of grass trait variation. To test this, we collected data on the community composition and trait variation of grasses (41 species) and grasshoppers (53 species) in 50 plots in a South African savanna. Structural equation models were used to investigate how the range and spacing of within-community functional trait values of both grasses and their insect herbivores (grasshoppers; Acrididae) respond to (1) rainfall and fire frequency gradients and (2) the trait similarity patterns of the other trophic level. The analyses revealed that traits of co-occurring grasses became more similar toward lower rainfall and higher fire frequency (environmental control), while showing little evidence for top-down control. Grasshopper trait range patterns, on the other hand, were mostly directly driven by vegetation structure and grass trait range patterns (bottom-up control), while environmental factors had mostly indirect effects via plant traits. Our study shows the potential to expand trait-based community assembly theory to include trophic interactions.

Neurocognitive disorders: cluster 1 of the proposed meta-structure for DSM-V and ICD-11.

BACKGROUND: In an effort to group mental disorders on the basis of aetiology, five clusters have been proposed. In this paper, we consider the validity of the first cluster, neurocognitive disorders, within this proposal. These disorders are categorized as 'Dementia, Delirium, and Amnestic and Other Cognitive Disorders' in DSM-IV and 'Organic, including Symptomatic Mental Disorders' in ICD-10. METHOD: We reviewed the literature in relation to 11 validating criteria proposed by a Study Group of the DSM-V Task Force as applied to the cluster of neurocognitive disorders. RESULTS: 'Neurocognitive' replaces the previous terms 'cognitive' and 'organic' used in DSM-IV and ICD-10 respectively as the descriptor for disorders in this cluster. Although cognitive/organic problems are present in other disorders, this cluster distinguishes itself by the demonstrable neural substrate abnormalities and the salience of cognitive symptoms and deficits. Shared biomarkers, co-morbidity and course offer less persuasive evidence for a valid cluster of neurocognitive disorders. The occurrence of these disorders subsequent to normal brain development sets this cluster apart from neurodevelopmental disorders. The aetiology of the disorders is varied, but the neurobiological underpinnings are better understood than for mental disorders in any other cluster. CONCLUSIONS: Neurocognitive disorders meet some of the salient criteria proposed by the Study Group of the DSM-V Task Force to suggest a classification cluster. Further developments in the aetiopathogenesis of these disorders will enhance the clinical utility of this cluster.

Neurodevelopmental disorders: cluster 2 of the proposed meta-structure for DSM-V and ICD-11.

BACKGROUND: DSM-IV and ICD-10 are atheoretical and largely descriptive. Although this achieves good reliability, the validity of diagnoses can be increased by an understanding of risk factors and other clinical features. In an effort to group mental disorders on this basis, five clusters have been proposed. We now consider the second cluster, namely neurodevelopmental disorders. METHOD: We reviewed the literature in relation to 11 validating criteria proposed by a DSM-V Task Force Study Group. RESULTS: This cluster reflects disorders of neurodevelopment rather than a 'childhood' disorders cluster. It comprises disorders subcategorized in DSM-IV and ICD-10 as Mental Retardation; Learning, Motor, and Communication Disorders; and Pervasive Developmental Disorders. Although these disorders seem to be heterogeneous, they share similarities on some risk and clinical factors. There is evidence of a neurodevelopmental genetic phenotype, the disorders have an early emerging and continuing course, and all have salient cognitive symptoms. Within-cluster co-morbidity also supports grouping these disorders together. Other childhood disorders currently listed in DSM-IV share similarities with the Externalizing and Emotional clusters. These include Conduct Disorder, Attention Deficit Hyperactivity Disorder and Separation Anxiety Disorder. The Tic, Eating/Feeding and Elimination disorders, and Selective Mutisms were allocated to the 'Not Yet Assigned' group. CONCLUSION: Neurodevelopmental disorders meet some of the salient criteria proposed by the American Psychiatric Association (APA) to suggest a classification cluster.

Inhibition of mammary tumorigenesis in carcinogen-treated Lewis rats by suppression of prolactin secretion.

One hundred sixty-eight female Lewis rats were treated intragastrically with 10 mg 7,12-dimethylbenz[a]anthracene at 56 and 63 days of age. Pituitary prolactin secretion was suppressed in one-half of these rats by daily sc administrations of 2-bromoergocryptine mesylate (CB-154; 0.4 mg/100 g body wt) from 29 to 90 days of age (series 1) and from 90 to 140 days of age (series 2). Treatment with CB-154 was initiated prior to the onset of palpable mammary carcinomas. Control rats were given injections of saline. Inguinal mammary glands were excised from 10 control and 10 CB-154-treated rats at the cessation of saline and CB-154 treatments and examined for hyperplastic nodules (HN). The remaining rats were palpated weekly for mammary carcinomas (MC) and killed at 200 days of age. Mean number of HN per rat, mean number of MC per rat, and percent of rats with MC were, respectively: series 1--controls, 0.6, 1.5, and 68; CB-154 treatment, 0.5, 1.1, and 62; series 2--controls, 10.4, 2.0, and 94; CB-154 treatment, 5.1, 1.1, and 56. The number of HN and MC was only slightly reduced in rats when prolactin was suppressed during carcinogen treatment (series 1) but markedly reduced when prolactin was suppressed after carcinogen treatment (series 2). These results provide evidence that prolactin is involved in the early development of mammary dysplasias in the carcinogen-treated female Lewis rat.

Effects of systemic recombinant interleukin-2 on natural killer and lymphokine activated killer activity of human tumor infiltrating lymphocytes.

The purpose of these studies was to compare local and systemic human lymphokine activated killer (LAK) and natural killer (NK) cytotoxicity and to determine its modulation by the systemic administration of recombinant interleukin-2 (rIL-2). After preoperative systemic rIL-2, we extracted tumor infiltrating lymphocytes (TIL) and peripheral blood lymphocytes (PBL) from patients with pulmonary tumors and compared pre- and posttreatment spontaneous NK activity and their response to in vitro rIL-2. Spontaneous TIL NK activity was increased in patients receiving 15,000 units/kg rIL-2 preoperatively [6.6 lytic units (LU)] compared to those receiving 1,000-10,000 units/kg (0.8 LU) or no rIL-2 (1.4 LU). After 3 days incubation with 1,000 units/ml rIL-2, TIL NK cytotoxic activity was increased in patients receiving 15,000 units/kg rIL-2 (65.4 LU) compared to those receiving 1,000-10,000 units/kg (6.0 LU) or no treatment (24.9 LU). Spontaneous TIL LAK activity was low overall (1.1 LU) with the exception of two patients receiving 15,000 units/kg who had 3.1 and 3.7 LU spontaneously. TIL LAK precursor activity was only slightly increased in patients receiving 1,000-10,000 units/kg rIL-2, whereas those receiving 15,000 units/kg rIL-2 had an average of 22.8 LU. Systemic rIL-2 also increased spontaneous PBL NK activity. Reincubation of PBL obtained at time of surgery or 3 days after discontinuing systemic rIL-2 resulted in significant increases in cytotoxic response to in vitro rIL-2 compared to pre-IL-2 in vitro responses. Systemic rIL-2 had no effect on spontaneous PBL LAK activity. Thus, the immunosuppressive tumor environment can be partially reversed with 15,000 units/kg systemic rIL-2. Higher doses of systemic rIL-2 also increased spontaneous PBL NK activity at time of surgery and 3 days after discontinuing rIL-2. Both TIL and PBL inducible cytotoxicity were boosted in vitro following higher doses of systemic rIL-2.

A Diffusion Tensor Imaging Study on White Matter Abnormalities in Patients with Type 2 Diabetes Using Tract-Based Spatial Statistics.

BACKGROUND AND PURPOSE: Patients with type 2 diabetes mellitus have considerably higher risk of developing cognitive impairment and dementia. WM changes in these patients have been reported. Our aim was to demonstrate that gradual and continuous WM change and the associated cognitive decline in patients with type 2 diabetes mellitus can be captured by DTI parameters, which can be used to complement neuropsychological test scores in identifying patients with type 2 diabetes mellitus with and without mild cognitive impairment. MATERIALS AND METHODS: Forty-two patients with type 2 diabetes mellitus, divided into a group with mild cognitive impairment (n = 20) and a group with normal cognition (n = 22), were enrolled with age-, sex-, and education-matched healthy controls (n = 26). 3T DTI followed by Tract-Based Spatial Statistics analysis was used to investigate the differences in fractional anisotropy, mean diffusivity, axial diffusivity (λ1), and radial diffusivity (λ23) among the groups. A receiver operating characteristic analysis assessed the performance of DTI parameters for separating the 2 groups with type 2 diabetes mellitus. RESULTS: The whole-brain Tract-Based Spatial Statistics analysis revealed that 7.3% and 24.9% of the WM exhibited decreased fractional anisotropy and increased mean diffusivity (P < .05), respectively, between the diabetes mellitus with mild cognitive impairment and the diabetes mellitus with normal cognition groups, while considerably larger WM regions showed fractional anisotropy (36.6%) and mean diffusivity (58.8%) changes between the diabetes mellitus with mild cognitive impairment and the healthy control groups. These changes were caused primarily by an elevated radial diffusivity observed in the patients with diabetes mellitus with mild cognitive impairment. Radial diffusivity also exhibited subtle but statistically significant changes between the diabetes mellitus with normal cognition and the healthy control groups. Analyses on individual fiber tracts showed pronounced fractional anisotropy reduction and mean diffusivity elevation in regions related to cognitive functions. The receiver operating characteristic analysis on the right cingulum (hippocampus) showed that fractional anisotropy produced a larger area under the curve (0.832) than mean diffusivity (0.753) for separating mild cognitive impairment from normal cognition among patients with type 2 diabetes mellitus. When fractional anisotropy was combined with mean diffusivity, the area under the curve was further improved to 0.857. CONCLUSIONS: DTI parameters can show a substantial difference between patients with type 2 diabetes mellitus with and without mild cognitive impairment, suggesting their potential use as an imaging marker for detecting cognitive decline in patients with type 2 diabetes mellitus. More important, DTI parameters may capture gradual and continuous WM changes that can be associated with early stages of cognitive decline in patients with type 2 diabetes mellitus before they can be diagnosed clinically by using conventional neuropsychological tests.

Distinct calcium signals in developing cortical interneurons persist despite disorganization of cortex by Tbr1 KO.

Cortical development involves the structuring of network features by genetically programmed molecular signaling pathways. Additionally, spontaneous ion channel activity refines neuronal connections. We examine Ca(2+) fluctuations in the first postnatal week of normal mouse neocortex and that expressing knockout of the transcription factor T-brain-1 (Tbr1): a signaling molecule in cortical patterning and differentiation of excitatory neurons. In cortex, glutamatergic neurons express Tbr1 just before the onset of population electrical activity that is accompanied by intracellular Ca(2+) increases. It is known that glutamatergic cells are disordered with Tbr1 KO such that normal laying of the cortex, with newer born cells residing in superficial layers, does not occur. However, the fate of cortical interneurons is not well studied, nor is the ability of Tbr1 deficient cortex to express normal physiological activity. Using fluorescent proteins targeted to interneurons, we find that cortical interneurons are also disordered in the Tbr1 knockout. Using Ca(2+) imaging we find that population activity in mutant cortex occurs at normal frequencies with similar sensitivity to GABAA receptor blockade as in nonmutant cortex. Finally, using multichannel fluorescence imaging of Ca(2+) indicator dye and interneurons labeled with red fluorescent protein, we identify an additional Ca(2+) signal in interneurons distinct from population activity and with different pharmacological sensitivities. Our results show the population activity described here is a robust property of the developing network that continues in the absence of an important signaling molecule, Tbr1, and that cortical interneurons generate distinct forms of activity that may serve different developmental functions. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 76: 705-720, 2016.

Factors affecting survival in superior sulcus tumors.

Fifty-five patients with superior sulcus syndrome were treated at the UCLA Medical Center and Wadsworth VA Hospital (Los Angeles) between 1956 and 1985. Twenty-eight underwent surgery, six of whom were found unresectable at the time of thoracotomy. Twenty-one of 22 in the resected group received preoperative irradiation. Twenty-seven patients received radiation only. Surgical morbidity was 21%, and there were two in-hospital deaths. Five-year survival for extended resection patients was 34%. The radiation only group had no 5-year survivors. Factors associated with a worse prognosis include positive margins, N2 disease, and vertebral body involvement. The best results for superior sulcus tumors are obtained by preoperative irradiation followed by en bloc resection of the tumor. In the event complete resection is impossible, radiation has a role in palliation of pain with occasional prolonged survival.

Morphologic and ultrastructural examination of I-A+ cells in the murine iris.

The surface membrane expression of major histocompatibility (MHC) class II antigens is an important prerequisite for presentation of foreign antigens to the immune system. Because particular antigens that are placed within the anterior chamber of the eye elicit a deviant form of immunity in which effector delayed-type hypersensitivity responses are suppressed, it has been proposed that novel MHC class II antigen-bearing cells exist in the tissues that line the anterior chamber. Class II MHC antigen expression has been identified within the iris, but the detailed morphologic description of these cells is incomplete. With the use of in situ immunoperoxidase and immunoelectron microscopic techniques, we examined the morphologic and ultrastructural characteristics of resident MHC-positive class II (I-A+) cells in murine irises. A significant number of these cells was found in the connective tissue of BALB/c irises. The majority showed extensive dendritic morphologic characteristics and formed a network throughout the iris that did not overlap. Ultrastructurally, I-A+ cells had an indented nucleus, some vacuoles, lysosomes, mitochondria, and an occasional phagosome within their cytoplasm and an absence of desmosomes or other intercellular junctions. Based on these features, it is unlikely that these cells are epithelial or endothelial in origin, but rather are similar to cells of the monocyte/macrophage/dendritic cell lineage. These results show the presence of an I-A+ dendritic cell population, within the murine iris, distributed in a pattern that is similar to that of Langerhans cells in the skin. Due to their compartmentalization within the eye, this cell population may represent a novel antigen-presenting cell that contributes to the immunologic privilege of the anterior chamber.

Prognostic implications of pulmonary satellite nodules: are the 1997 staging revisions appropriate?

In the 1992 AJCC and 1993 UICC staging systems, primary lobe satellite nodules increased the T designation of the primary by one level and ipsilateral non-primary lobe satellite nodules raised the T designation to T4. The recent 1997 UICC and AJCC staging revisions assign a T4 (IIIb) designation to satellite nodules in a primary lobe, and a M1 (IV) designation to satellites in ipsilateral non-primary lobes. There is abundant evidence showing that satellite nodules are negative prognostic factors, but their inclusion in stage IIIb and IV may not be appropriate. The English-language medical literature was searched for papers reporting survival after surgical resection of lung cancer with satellite nodules (primary and non-primary ipsilateral lobe locations). Eleven articles were retrieved and their data pooled for analysis. Of 568 resected patients with satellite nodules, actuarial 5-year survival was 20%. Five articles gave separate survival data for satellite nodules in primary versus ipsilateral non-primary lobes. All five articles showed better survival for satellite nodules in a primary lobe. Satellite nodules in a primary lobe have a better prognosis than those in ipsilateral non-primary lobes. Survival for resected lung cancer with satellite nodules in a primary lobe is better than that usually observed for T4 (IIIB) disease. The 1997 staging revisions may unduly upstage patients with satellite nodules in a primary cancer lobe. However, satellite nodules in ipsilateral non-primary lobes share metastatic mechanisms and have survival results consistent with M1 stage disease. Their 1997 MI designation may be appropriate.

Comparison of human lung cancer/SCID mouse tumor xenografts and cell culture growth with patient clinical outcomes.

Leukemic cell growth in SCID mice has been reported as a predictor of disease relapse. However, there is a paucity of literature regarding xenograft growth and clinical outcomes in non-small cell lung cancer (NSCLC). Seventy-nine specimens from patients with NSCLC were either subcutaneously implanted into SCID mice and/or placed in tissue culture. Retrospective chart review was correlated with stage, histology, necrosis, disease-free interval, and survival. Tumor xenografts were successfully established with 17 of 37 (46%) tumor biopsy tissues. Thirteen of 59 (22%) specimens grew in cell culture. Patients whose tumors grew in SCID mice had no difference in survival compared to those with no growth ( n=20, p=0.42). Median survival was 36 months in 13 patients whose tumors grew in cell culture compared to 39 months in 46 patients without growth. Eight of 12 (67%) patients with metastasis showed SCID/human xenograft growth, whereas nine of 25 (36%) without metastases did so ( p=0.08). Growth of tumor cells in vitro occurred in 11 of 31 (35%) adenocarcinomas, one of 25 (4%) squamous cell carcinomas, and one of three (33%) large cell carcinomas ( p=0.02). Well or moderately differentiated tumors grew in cell culture in only two of 22 (9%), whereas poorly or undifferentiated tumors grew in 11 of 32 (34%) cases ( p=0.03). We conclude that neither the ability of a tumor to engraft and grow in SCID mice nor its ability to grow in vitro in cell culture is a reliable predictor of disease outcome or survival in patients with NSCLC. The ability to propagate tumors in vitro appears to be more dependent upon the histological type of tumor and its degree of differentiation.

Natural killer activity of lymphocytes infiltrating human lung cancers following preoperative systemic recombinant interleukin 2.

Tumor-infiltrating lymphocytes (TILs) show depressed natural killer (NK) activity compared with peripheral blood lymphocytes (PBLs). To determine if TIL NK function can be reactivated in vivo, 11 patients with tumors metastatic to the lung were treated with systemic recombinant interleukin 2 (rIL-2). Spontaneous TIL NK activity and NK activity after three days' incubation with 100 U/mL of rIL-2 were increased in patients receiving 15,000 U/kg of rIL-2 preoperatively compared with those receiving between 1000 and 10,000 U/kg. Histologically, higher doses of rIL-2 increased the number of intratumoral lymphocytes, the level of peritumoral lymphocytic transferrin, and the expression of HLA-DR. Spontaneous PBL NK activity in patients receiving between 10,000 and 15,000 U/kg of rIL-2 was also increased and was further increased by in vitro culture with rIL-2. Thus, PBL NK activity and TIL NK function in vivo can be augmented with 15,000 U/kg of systemic rIL-2. Both TIL- and PBL-inducible cytotoxicities were further enhanced by in vitro culture with rIL-2.

Use of pleura, azygos vein, pericardium, and muscle flaps in tracheobronchial surgery.

Desmoplastic reactions secondary to adjuvant chemotherapy and radiation in stage IIIA lung cancer, plus advances in complex tracheobronchial surgery, have rejuvenated an interest for augmenting bronchial stump coverage and suture line reinforcement. We present the techniques and applications of harvesting pleural, azygos vein, pericardial flaps, and fat pad grafts, and intrathoracic transposition of chest wall muscle flaps.

Surgical technique and application of pericardial fat pad and pericardiophrenic grafts.

Oncologic developments in stage IIIA lung cancer and complex tracheal reconstruction have renewed interest in bronchial stump and tracheal coverage. The surgical techniques to mobilize and apply pericardial fat pad and pericardiophrenic grafts are discussed.

Sternal resection and reconstruction.

Twenty-one patients underwent sternal resection and reconstruction. Surgical indications included sternal infection in 9 patients, recurrent breast cancer in 6, metastatic carcinoma from an unknown primary in 2, pectus excavatum in 2, and osteogenic sarcoma and eosinophilic granuloma in 1 each. Management included partial sternectomy in 10 patients (group 1) and complete sternectomy in 11 (group 2). Chest wall reconstruction was by various flaps and mesh repairs. Blood transfusions averaged 2 units in group 1 versus 5.5 units in group 2 (p = 0.02). Average number of days until extubation was 2.6 in group 1 versus 7.3 in group 2 (p = 0.04). Average number of intensive care unit days was 4.4 for group 1 versus 9.4 for group 2 (p = 0.03). The number of days until discharge was 14 days for group 1 versus 20 days for group 2. Complications occurred in 40% of group 1 and 82% of group 2 patients. Overall mortality was 9.5%. Sternal resection and reconstruction, particularly complete sternal resections, are a major undertaking with substantial morbidity. Using a multidisciplinary approach (cardiothoracic, plastic and reconstructive, critical care medicine, and infectious disease) and aggressive pulmonary support, acceptable cosmetic and functional results are possible.

Thoracic approaches to anterior spinal operations: anterior thoracic approaches.

We performed a retrospective review of 36 patients aged 23 to 71 years (mean age, 52 years) who underwent 46 operations through a thoracic or thoracolumbar approach for orthopedic or neurosurgical procedures at Emory University Affiliated Hospitals. Pathologic indications for operation were metastatic disc disease in 10, herniated nucleus pulposus in 11, osteomyelitis in 6, vertebral fracture in 2, spinal deformities in 4, spinal abscess in 1, Pott's disease in 1, and liposarcoma in 1. Major indications for operation were infection and progressive paraparesis or paresthesias. Surgical approach consisted of a posterior lateral thoracotomy in 23, thoracotomy with retroperitoneal exposure in 6, thoracoabdominal exposure in 4, and cervical/upper sternotomy in 3. Diaphragmatic mobilization was required in 12. Surgical approach is dictated by the level of the lesion and its length. Lesions of T1 to T6 are approached through an upper sternotomy or right thoracotomy; lesions of T6 to L3, through a left thoracotomy with or without diaphragmatic mobilization. Specific techniques of segmental vessel division, diaphragmatic mobilization, and evaluation of artery of Adamkiewicz are emphasized. Rib grafts are harvested as needed. The thoracic surgeon can greatly enhance preoperative assessment, operative exposure and closure, and postoperative care for patients undergoing thoracotomy for spinal conditions.

Salvage of colon interposition by antethoracic free jejunal transfer.

Intrathoracic disruption of an esophagocolonic anastomosis after colon interposition can be a fatal complication. A case is presented in which an antethoracic free jejunal transfer achieved successful salvage. The patient returned to oral alimentation with no functional impairment.

Sternal release and advancement with thoracotomy and osteotomy for idiopathic osteopenia.

Transient neurologic changes developed in a rare case of progressive thoracic kyphosis secondary to idiopathic osteopenia with marked spinal and chest cage deformities. The patient underwent correction by both anterior thoracic and posterior spinal approaches, with concomitant sternal release and advancement. After 16 months he continues to have good anatomic and functional results.

Malignant pleural mesothelioma: a problematic review.

Malignant pleural mesothelioma is a rare tumor that has been difficult to study. Because of disappointing treatment results, malignant pleural mesothelioma has remained an area of active research and development. A clinicopathologic review is performed in light of several problematic issues involving diagnosis, staging, natural history, and treatment. Multimodality treatment with surgery followed by adjuvant local and systemic therapy remains the most optimal therapy. Many controversial issues still exist in the treatment of malignant pleural mesothelioma. In the ensuing years newer staging systems, better preoperative staging, newer experimental therapies, and the localization of patients at expert centers will undoubtedly have an impact on disease management.