Preface

The legal process is often invoked to resolve scientific or economic problems such as may arise when a bridge collapses, or an aeroplane crashes, or a ship sinks; or when a mishap occurs on the operating table; or when patent protection is sought for an invention claimed to be novel; or when it is necessary to assess the effect of a commercial practice on competition in a market; or when a baby dies, for no apparent reason, in its cot; or when it is sought to identify a fingerprint on a murder weapon.     

Regulation of intracellular pH

The approach that most animal cells employ to regulate intracellular pH (pH(i)) is not too different conceptually from the way a sophisticated system might regulate the temperature of a house. Just as the heat capacity (C) of a house minimizes sudden temperature (T) shifts caused by acute cold and heat loads, the buffering power (beta) of a cell minimizes sudden pH(i) shifts caused by acute acid and alkali loads. However, increasing C (or beta) only minimizes T (or pH(i)) changes; it does not eliminate the changes, return T (or pH(i)) to normal, or shift steady-state T (or pH(i)). Whereas a house may have a furnace to raise T, a cell generally has more than one acid-extruding transporter (which exports acid and/or imports alkali) to raise pH(i). Whereas an air conditioner lowers T, a cell generally has more than one acid-loading transporter to lower pH(i). Just as a house might respond to graded decreases (or increases) in T by producing graded increases in heat (or cold) output, cells respond to graded decreases (or increases) in pH(i) with graded increases (or decreases) in acid-extrusion (or acid-loading) rate. Steady-state T (or pH(i)) can change only in response to a change in chronic cold (or acid) loading or chronic heat (or alkali) loading as produced, for example, by a change in environmental T (or pH) or a change in the kinetics of the furnace (or acid extrudes) or air conditioner (or acid loaders). Finally, just as a temperature-control system might benefit from environmental sensors that provide clues about cold and heat loading, at least some cells seem to have extracellular CO(2) or extracellular HCO(3)(-) sensors that modulate acid-base transport.     

Royal College of Physicians and Surgeons of Canada: annual meeting draws over 2000 physicians

In a review of 19 years'' experience with inhalation of foreign bodies by children the 33 patients (mean age 28 months) were found to have presented most frequently with wheezing or coughing, or both, of recent onset, and to have decreased air entry, rhonchi or respiratory stridor, or a combination of these signs. Eighteen children had inhaled a nut, a pea or a bean. The other 15 had inhaled various organic and inorganic objects. All the children underwent bronchoscopy, and the foreign body was completely removed in 19 during the first procedure; the remainder required repeated bronchoscopy or direct surgical removal of the foreign body, or both. Permanent disability or death was not encountered. The findingsof the study indicate that early bronchoscopic removal is the preferred treatment when a child inhales a foreign body.     

Nucleolipids: natural occurrence, synthesis, molecular recognition, and supramolecular assemblies as potential precursors of life and bioorganic materials

Nucleolipids are hybrid molecules composed of a nucleobase, a nucleoside, a nucleotide or an oligonucleotide (either DNA or RNA), and a lipophilic moiety, which might be either simply a single- or double-chained alkyl (or alkenyl) moiety or a carbocyclic hydrocarbon such as cholesterol, a vitamin, or a bile acid. This review covers all aspects of nucleolipids, namely their natural occurrence, their synthesis, their molecular recognition, as well as aggregation behavior, either in aqueous or non-aqueous solution. Potential future aspects of nucleolipids in material sciences and for the elucidation of biochemical reactions in living cells are discussed.     

A clinical approach to common electrolyte problems: 2. Potassium imbalances.

A clinical approach to potassium imbalances is presented. Hypokalemia is rarely due solely to a reduced intake of potassium; instead, it usually results from a potassium flux into the cells or increased loss of the element, at times combined with a decreased intake. The clinician must seek the cause of the intracellular flux or the source of the gastrointestinal or renal loss. The causes of gastrointestinal losses are generally self evident. Renal potassium wasting, though, generally results from increased mineralocorticoid activity, an increased rate of urinary flow or of sodium delivery to the distal nephron, or both, hypomagnesemia or a combination of these factors. Hyperkalemia may be factitious, but usually it is caused by a flux of potassium from the cells or a decrease in the renal loss of potassium, the latter being mediated by a reduction in renal function, mineralocorticoid activity, or the rate of urinary flow or sodium delivery, or both. In both hypokalemia and hyperkalemia, treatment must be guided by the specific clinical circumstances.     

Symposium on diarrhea. 2. Clinical diagnosis of the causes of diarrhea.

Elucidation of the cause of diarrhea is facilitated by considering which of three principal determinants are of relevance in a particular case. These determinants relate to the onset (whether diarrhea is acute or chronic), to infection or an absence ofinfection and to the presence in the stool of blood or mucus, or both. Diagnosis is also facilitated by taking an accurate and full history, conducting a physical examination, performing sigmoidoscopy and, with proper care, attempting a therapeutic diagnosis. Findings from investigations should then enable one to arrive at a diagnosis. The diagnosis can be reached in an orderly fashion by classifying the types of diarrhea into eight categories: with respect to the acute or chronic onset a case of diarrhea may be noninfectious, without blood or mucus in the stool; noninfectious, with blood or mucus, or both; infectious, without blood or mucus; and infectious, with blood or mucus in the stool.     

KATP channels and myocardial preconditioning: an update

Ischemic or myocardial preconditioning (IPC) is a phenomenon whereby brief periods of ischemia have been shown to protect the myocardium against a more sustained ischemic insult. The result of IPC may be manifest as a marked reduction in infarct size, myocardial stunning, or incidence of cardiac arrhythmias. Whereas many endogenous neurotransmitters, peptides, and hormones have been proposed to play a role in the signal transduction pathways mediating the cardioprotective effect of IPC, nearly universal evidence indicates the involvement of the ATP-sensitive potassium (KATP) channel. Initial evidence suggested that the surface or sarcolemmal KATP (sarcKATP) channel triggered or mediated the cardioprotective effects of IPC; however, more recent findings have suggested a major role for a mitochondrial site or possibly a mitochondrial KATP channel (mitoKATP). This review presents evidence that supports a role for these two channels as a trigger and/or downstream mediator in the phenomenon of IPC or pharmacologically induced PC as well as recent evidence that suggests the involvement of a mitochondrial calcium-activated potassium (mitoKca) channel or the electron transport chain in mediating the beneficial effects of IPC or pharmacologically induced PC.     

Protein tagging and detection with engineered self-assembling fragments of green fluorescent protein

Existing protein tagging and detection methods are powerful but have drawbacks. Split protein tags can perturb protein solubility or may not work in living cells. Green fluorescent protein (GFP) fusions can misfold or exhibit altered processing. Fluorogenic biarsenical FLaSH or ReASH substrates overcome many of these limitations but require a polycysteine tag motif, a reducing environment and cell transfection or permeabilization. An ideal protein tag would be genetically encoded, would work both in vivo and in vitro, would provide a sensitive analytical signal and would not require external chemical reagents or substrates. One way to accomplish this might be with a split GFP, but the GFP fragments reported thus far are large and fold poorly, require chemical ligation or fused interacting partners to force their association, or require coexpression or co-refolding to produce detectable folded and fluorescent GFP. We have engineered soluble, self-associating fragments of GFP that can be used to tag and detect either soluble or insoluble proteins in living cells or cell lysates. The split GFP system is simple and does not change fusion protein solubility.     

Autism Spectrum Disorder Initiation by Inflammation-Facilitated Neurotoxin Transport

Autism spectrum disorders have been linked to genetics, gut microbiota dysbiosis (gut dysbiosis), neurotoxin exposures, maternal allergies or autoimmune diseases. Two barriers to ingested neurotoxin transport into the central nervous system of a fetus or child are the gastrointestinal wall of the mother or child and the blood–brain barrier of the fetus or child. Inflammation from gut dysbiosis or inflammation from a disease or other agent can increase the gastrointestinal wall and the blood–brain barrier permeabilities to enable neurotoxins to reach the brain of a fetus or child. Postnatal gut dysbiosis is a particular inflammation risk for autism spectrum disorders caused by neurotoxin transport into a child's brain. An extensive gut dysbiosis or another source of inflammation such as a disease or other agent in combination with neurotoxins, including aluminum, mercury, lead, arsenic, cadmium, arsenic, organophosphates, and neurotoxic bacterial toxins and fungal toxins resulting from the gut dysbiosis, can elevate neurotoxin levels in a fetal or child brain to cause neurodevelopmental damage and initiate an autism spectrum disorder. The neurotoxins aluminum and mercury are especially synergistic in causing neurodevelopmental damage. There are three plausible causational pathways for autism spectrum disorders. They include inflammation and neurotoxin loading into the fetal brain during the prenatal neurodevelopment period, inflammation and neurotoxin loading into the brain during the postnatal neurodevelopment period or a two-stage loading of neurotoxins into the brain during both the prenatal and postnatal neurodevelopment periods.

     

Lectotypifications and new combinations for Flora Nordica Vol. 1 (Lycopodiaceae–Papaveraceae)

Names of 34 taxa based on Nordic or Arctic material are lecto- or, in a few cases, neo-typified, published as new combinations or, discussed because of a change of basionym or other reasons.–Flora Nordica note No. 18.     

Determining the waist circumference in african americans which best predicts insulin resistance

Total body size and central fat distribution are important determinants of insulin resistance. The BMI and waist circumference (WC) thresholds in African Americans that best predict insulin resistance are unknown. Our goal was to determine the BMI and WC values in African Americans, which optimally predict insulin resistance. The subjects were African Americans (68 men, 63 women), aged 35 +/- 8 years (mean +/- s.d.), with a BMI of 30.9 +/- 7.5, in the range of 18.5-54.7 kg/m(2), and with a WC of 98 +/- 18, in the range of 69-173 cm. Insulin resistance was defined by the lowest tertile of the insulin sensitivity index (S(I)). The Youden index was calculated to determine the WC and BMI thresholds that predict insulin resistance with an optimal combination of sensitivity and specificity. In men the thresholds that optimally predicted insulin resistance were a BMI > or =30 kg/m(2) or a WC > or =102 cm. For women, insulin resistance was best predicted by a BMI > or =32 kg/m(2) or a WC > or =98 cm. In African Americans, insulin resistance (in men) was best predicted by a WC > or =102 cm, and in women by a WC > or =98 cm, or by a BMI value that fell in the obese category (men: > or =30 kg/m(2), women: > or =32 kg/m(2)).     

Multiple resins for analysis of amino acids and ninhydrin-positive compounds in hydrolyzates and physiological fluids

The newly available spherical cation-exchange resins HP-AN 90 and HP-B 80 are capable of performing various analyses of amino acids and peptides at low backpressures. These multipurpose resins can perform: a 2 or 4 hr simple (approximately 20 amino acids) procedure used with protein hydrolyzates, or a complex (50 or more amino acids) technical procedure (for physiological fluids), or a rapid screening procedure dealing with specific amino acids as they relate to clinical disease or biomedical studies, or the analysis of peptide samples.     

Couple-stress moduli of a trabecular bone idealized as a 3D periodic cellular network

Trabecular bone is modeled as a cellular material with an idealized periodic structure made of open cubic cells, which is effectively orthotropic. We evaluate apparent couple-stress moduli of such a periodic material; apparent moduli refer to the moduli obtained using a domain smaller than a Representative Volume Element and they depend on boundary conditions. We conduct this analysis computationally (using ANSYS) by subjecting a unit cell of this periodic cellular material to either displacement or traction boundary conditions. Cell walls, representing bone tissue, and void space, representing bone marrow, are both modeled and they are assumed to be linear elastic. The applied loadings include a uniaxial extension (or uniaxial stress), a hydrostatic deformation (or hydrostatic stress) and a shear deformation (or shear stress) to evaluate the first stiffness (or compliance) tensor, and an applied curvature (or bending moment), a uniaxial twist (or torsion), and a triaxial twist (or triaxial torsion) to evaluate the second couple-stress stiffness (or compliance) tensor. Apparent couple-stress moduli are computed by equating the total strain energy stored in the unit cell with the energy of an equivalent homogeneous orthotropic couple-stress material for each applied loading. The moduli computed using displacement boundary conditions give upper bound, while those obtained using traction boundary conditions give lower bound on effective couple-stress moduli. These bounds are very wide due to a large mismatch in elastic moduli of bone tissue and bone marrow. These results are in agreement with our studies on composite materials with very stiff or very compliant inclusions.     

C-ME: a 3D community-based, real-time collaboration tool for scientific research and training

The need for effective collaboration tools is growing as multidisciplinary proteome-wide projects and distributed research teams become more common. The resulting data is often quite disparate, stored in separate locations, and not contextually related. Collaborative Molecular Modeling Environment (C-ME) is an interactive community-based collaboration system that allows researchers to organize information, visualize data on a two-dimensional (2-D) or three-dimensional (3-D) basis, and share and manage that information with collaborators in real time. C-ME stores the information in industry-standard databases that are immediately accessible by appropriate permission within the computer network directory service or anonymously across the internet through the C-ME application or through a web browser. The system addresses two important aspects of collaboration: context and information management. C-ME allows a researcher to use a 3-D atomic structure model or a 2-D image as a contextual basis on which to attach and share annotations to specific atoms or molecules or to specific regions of a 2-D image. These annotations provide additional information about the atomic structure or image data that can then be evaluated, amended or added to by other project members.     

ADRENOCORTICAL TUMORS

Hormonally active tumors of the adrenal cortex are either benign adenomas or adenocarcinomas. They may be located within the adrenal gland or as adrenal rests along the Wolffian tract. Hyperplastic cortical tissue without actual neoplastic formation is also capable of elaborating excessive cortical secretions.At the present state of knowledge, any one or a combination of the following compounds may be elaborated in a given case: the electrolytic, glucogenic, androgenic, or estrogenic corticosteroids.Whether or not Cushing''s syndrome is primarily pituitary or adrenal in origin is still a matter of conjecture.     

Information spiraling: Movement of bacteria and their genes in streams

Bacteria in transport in streams are largely derived from other parts of the ecosystem. Here we review factors that influence transport of bacteria and their movement between habitats (such as sediment, water column, rocks, wood, and leaves) and consider the role of these movements in ecosystem processes. Bacteria enter the water column by sloughing, scouring, as a consequence of changes in morphology or hydrophobicity, or dislodgment by invertebrates and fish or other aquatic vertebrates. Transported cells (which may be planktonic or particle-associated) that colonize surfaces may establish new gene pools through cell division (vertical transfer) or genetic exchange (lateral transfer). Genetic information is also transported in streams as free or protected DNA or in bacteriophages. Movement of these vectors causes genetic information to spiral along a stream in a manner analogous to that of nutrients and organic carbon. Spiraling refers to the pattern of transport, uptake or attachment, and release of a molecule or cell. The flow of water in streams causes this cycle of attachment and release to be displaced downstream resulting in a spiral rather than a closed, stationary loop. Offprint requests to: L. G. Leff.     

Sudan Black B And Acetocarmine as a Combination Stain

Epidermis stripped from either fresh or fixed plant organs, or sections of paraffin-embedded or fresh material are placed on a slide and covered with a drop or two of iron-acetocarmine. The stain is intensified by warming the slide over a flame. After a few minutes a drop or two of a saturated solution of Sudan black B in 45% acetic acid is added and a cover slip applied. The preparations cannot be made permanent, but last a few weeks if sealed with a compound such as gum mastic-paraffin, or if the combined stain is drained off and a drop of Karo syrup is added before the cover slip is applied. The acetocarmine produces its usual staining effects, i.e., nuclei dark red and some components of the cytoplasm of certain cells a less intense red. The Sudan black B colors lipid structures an intense blue.     

Cardiac Wnt5a and Wnt11 promote fibrosis by the crosstalk of FZD5 and EGFR signaling under pressure overload

Progressive cardiac fibrosis accelerates the development of heart failure. Here, we aimed to explore serum Wnt5a and Wnt11 levels in hypertension patients, the roles of Wnt5a and Wnt11 in cardiac fibrosis and potential mechanisms under pressure overload. The pressure overload mouse model was built by transverse aortic constriction (TAC). Cardiac fibrosis was analyzed by Masson’s staining. Serum Wnt5a or Wnt11 was elevated and associated with diastolic dysfunction in hypertension patients. TAC enhanced the expression and secretion of Wnt5a or Wnt11 from cardiomyocytes (CMs), cardiac fibroblasts (CFs), and cardiac microvascular endothelial cells (CMECs). Knockdown of Wnt5a and Wnt11 greatly improved cardiac fibrosis and function at 4 weeks after TAC. In vitro, shWnt5a or shWnt11 lentivirus transfection inhibited pro-fibrotic effects in CFs under mechanical stretch (MS). Similarly, conditional medium from stretched-CMs transfected with shWnt5a or shWnt11 lentivirus significantly suppressed the pro-fibrotic effects induced by conditional medium from stretched-CMs. These data suggested that CMs- or CFs-derived Wnt5a or Wnt11 showed a pro-fibrotic effect under pressure overload. In vitro, exogenous Wnt5a or Wnt11 activated ERK and p38 (fibrotic-related signaling) pathway, promoted the phosphorylation of EGFR, and increased the expression of Frizzled 5 (FZD5) in CFs. Inhibition or knockdown of EGFR greatly attenuated the increased FZD5, p-p38, and p-ERK levels, and the pro-fibrotic effect induced by Wnt5a or Wnt11 in CFs. Si-FZD5 transfection suppressed the increased p-EGFR level, and the fibrotic-related effects in CFs treated with Wnt5a or Wnt11. In conclusion, pressure overload enhances the secretion of Wnt5a or Wnt11 from CMs and CFs which promotes cardiac fibrosis by activation the crosstalk of FZD5 and EGFR. Thus, Wnt5a or Wnt11 may be a novel therapeutic target for the prevention of cardiac fibrosis under pressure overload.Subject terms: Heart failure, Translational research     

Risk Assessment Applications Beyond Baseline Risks and Clean-Up Goals

Historically, the phrase “Risk Assessment” brought to mind a thick Superfund-type baseline risk assessment or clean-up goal derivation document filled with pages of tables with endless seemingly unrelated algorithms and numbers. Over the last decade, the principles of risk and exposure assessment have gained wide-reaching acceptance and are increasingly utilized to help solve other environmental impact, occupational health, or risk mitigation design problems. The typical objective of the classic risk assessment is the evaluation of current or future risks from exposure to contaminated media within the framework of a regulatory waste management or remediation program. Risk-based techniques are increasingly being used on a voluntary basis (i.e., outside of the standard regulatory arena) to demonstrate the presence, absence, or extent of environmental or health-related concerns in specific exposure circumstances. Likewise, a risk or exposure evaluation may be useful in determining the need for, or the legitimacy of, a public health advisory, alone or in conjunction with remedial or mitigative actions. Finally, risk-based techniques often find their way into the courtroom. Three case studies are presented in which riskbased solutions were employed to assist in resolving environmental or health-related issues: (1) a reversal of a fish consumption advisory; (2) an evaluation of arsenic in soil on and adjacent to a school facility; and (3) a challenge to a case of alleged methyl bromide exposure in a litigation context. In each case, the use of risk assessment principles was employed beyond the classic baseline risk assessment to address an applied problem of toxicological significance.     

Problems related to the diagnosis of Chagas' disease

Trypanosoma cruzi may be transmitted to a susceptible human through different routes: a superficial lesion in the skin, such as a scraping of the small wound produced by the hematophagous triatomid bug vector, which becomes infected with its contaminated feces; the placenta, from the infected mother to the product of conception; a transfusion from an infected donor, or even by ingestion of diverse foods infected or contaminated with the parasite. Whichever may be the transmission of the protozoon, it is advisable to have in mind that it is able to produce an asymptomatic or a symptomatic infection, being possible in both cases, using appropriated methods, to detect the T. cruzi and/or the antibodies generated. From the clinical stand-point, Chagas' Disease may present itself as acute or as a chronic disease. Habitually, the acute disease is characterized by general involvement, fever, hepato-splenomegaly, polidenopathy, and occasionally myocarditis and/or encephalitis, whereas, the chronic form of the disease is characterized by presenting itself in an isolated way or combined, chronic myocardiopathy, megaesophagous or megacolon. At any rate, the problems center in the possibility of a reasonable diagnostic assurance which permits the adoption of adequate therapeutic measures. Some facts, which may help to confront these problems are: a) The epidemiological antecedents (origin in an endemic area, personal knowledge of the vector or of being bitten by it, whether the mother or other relatives are affected by the disease, etc.).(ABSTRACT TRUNCATED AT 250 WORDS)