Effects of chloroquine, amodiaquine and pyrimethamine-sulfadoxine on Plasmodium falciparum gametocytemia

The effects of chloroquine, amodiaquine and pyrimethamine-sulfadoxine (SP) (Fansidar) on the infection rate and density of Plasmodium falciparum gametocytes were studied in 198 patients with falciparum malaria from an area in the Punjab where malaria is endemic but seasonally transmitted. One month following treatment of 100 patients, SP had reduced the gametocyte carrier rate from 37% to 6% and the mean gametocyte density from 80 to 1.4 per mm3 of blood. Chloroquine and amodiaquine were much less effective. Since SP has no gametocytocidal properties and the reduction in gametocytes coincided with clearance of asexual parasitemias, gametocytes were probably reduced subsequent to the cure of the asexual malaria infections. If used during the nontransmission season, SP might be an effective component of an integrated program for reducing malaria transmission in the Punjab and other areas where 4-aminoquinoline-resistant and SP-sensitive falciparum malaria exists.     

Hyperspectral interference tomography of nacre

Structural characterization of biologically formed materials is essential for understanding biological phenomena and their enviro-nment, and for generating new bio-inspired engineering concepts. For example, nacre—the inner lining of some mollusk shells—encodes local environmental conditions throughout its formation and has exceptional strength due to its nanoscale brick-and-mortar structure. This layered structure, comprising alternating transparent aragonite (CaCO₃) tablets and thinner organic polymer layers, also results in stunning interference colors. Existing methods of structural characterization of nacre rely on some form of cross-sectional analysis, such as scanning or transmission electron microscopy or polarization-dependent imaging contrast (PIC) mapping. However, these techniques are destructive and too time- and resource-intensive to analyze large sample areas. Here, we present an all-optical, rapid, and nondestructive imaging technique—hyperspectral interference tomography (HIT)—to spatially map the structural parameters of nacre and other disordered layered materials. We combined hyperspectral imaging with optical-interference modeling to infer the mean tablet thickness and its disorder in nacre across entire mollusk shells from red and rainbow abalone (Haliotis rufescens and Haliotis iris) at various stages of development. We observed that in red abalone, unexpectedly, nacre tablet thickness decreases with age of the mollusk, despite roughly similar appearance of nacre at all ages and positions in the shell. Our rapid, inexpensive, and nondestructive method can be readily applied to in-field studies.

Complex optical phenomena can emerge from a variety of biological or bio-inspired processes, from arrays of colors in peacocks (1) and other birds (2), butterflies (3), and opals (4), to the metal-like sheen of herring (5) and unique polarization-dependent properties of jewel beetles (6) and Pollia fruit (7). Nacre, or mother-of-pearl, is a prominent biologically formed mineral structure found throughout our oceans. It lines the inside of the shells formed by many mollusks, including bivalves, cephalopods, and gastropods. It features brilliant iridescent colors (Fig. 1) and is studied and emulated in part because of its outstanding mechanical performance (8, 9). The striking, colorful appearance of nacre has been a source of scientific curiosity since the days of Brewster (10), Rayleigh (11), and Raman (12, 13), and is the product of optical interference resulting from multiple interface reflections as light propagates through its stratified structure comprising stacks of transparent polygonal aragonite tablets (CaCO₃) interspersed with organic polymer (chitin and proteins) layers (14–16) (Fig. 1A). Nacre is one of seven mollusk shell structures (17). In the nacre structure, the aragonite tablets are typically 5 to 10 μm in diameter and hundreds of nanometers thick [200 to 1,100 nm across all shells, and 250 to 500 nm in red abalone (18)], while the organic sheets are an order of magnitude thinner (14, 16, 19). In columnar nacre formed by gastropods like abalone and snails (Fig. 1), co-oriented tablets are stacked on top of one another, while in sheet nacre formed by bivalves like pearl oysters and pen shells, co-oriented tablets are staggered diagonally (18) (see Movie S1 for an animation showing how co-oriented tablets are stacked in columnar nacre). Despite the significant structural and formation–mechanism differences, the thicknesses of tablets and organic layers are similar in columnar and sheet nacre, and so are the optical and mechanical behavior (20). The resulting palette of colors is primarily dependent on the nacre tablet thickness and the viewing angle, and the optical response that yields these colors can be understood as that of a Bragg reflector (21) with disorder in the layer thicknesses, where the optical band gaps are determined by the thicknesses of the transparent layers (5, 22, 23). Thus, the spectrum of light reflected from a nacre surface encodes information about its physical structure (Fig. 1 B–D).Open in a separate windowFig. 1.(A) Nacre, the colorful iridescent inner lining of some mollusk shells. Here, the red abalone, or H. rufescens, shell features columnar nacre, which comprises thousands of layers of polygonal aragonite tablets interspersed with organic sheets. (B) A close-up photograph of the nacre surface shows a variety of colors and nonuniformities. (C and D) Given a broadband white light source illuminating nacre at a fixed angle of incidence, variations in color are observed due to the difference in average thickness of aragonite tablets comprising nacre. (E) Hyperspectral interference tomography (HIT) setup: A hyperspectral camera collects predominantly specular reflectance data across a sample illuminated by a collimated source at a fixed angle of incidence from the normal to the sample (θ). The reflected light is polarized using a wire-grid polarizer. (F) A color photograph of a region of nacre that was analyzed. (G) Map of the mean tablet thickness (MTT) obtained using HIT, overlaid on a grayscale rendering of the photograph in F. Highlighted in red is a 5 × 5-mm region used to analyze the ontogeny of nacre in Fig. 4. The region around this area was masked off using opaque tape, which is highlighted with the dashed white box.Understanding and characterizing the structure of nacre and other biomaterials have deep and surprising implications. For example, the average thickness of the tablets comprising ancient nacre can be used as a proxy for local ocean temperatures at the time of nacre formation, enabling paleoclimatology spanning hundreds of millions of years (18, 24, 25). The structure of nacre is also an inspiration for engineered materials thousands of times stronger than the constituent materials (15, 26, 27). To that end, new techniques have been developed to probe and understand the structure of nacre, such as polarization-dependent imaging contrast (PIC) mapping using X-ray absorption near-edge structure spectroscopy combined with photoemission electron spectromicroscopy (18, 28, 29), or X-ray nanotomography (30). However, these characterization techniques such as cross-sectional electron microscopy result in the destruction of the sample and are time-consuming and costly.Here, we present a method for rapid, nondestructive, and large-scale structural characterization of disordered and nonuniform stratified thin-film materials and apply it to the analysis of nacre. Our all-optical method employs hyperspectral imaging combined with thin-film modeling to extract nacre mean tablet thicknesses (MTTs) and tablet degree of disorder (σ)—defined as the standard deviation of the thicknesses—across large areas (Fig. 1 E–G). This characterization method is designated as hyperspectral interference tomography (HIT). We used HIT to map the structure of mollusk shell nacre across many stages of development and identified a previously unexplored relationship between the age of the organism and the structure of the nacre layer. We investigated two particular species of nacre-forming mollusks, Haliotis rufescens (red abalone) and Haliotis iris (paua, or rainbow abalone; data only in SI Appendix), for which the aragonite tablet thicknesses lie within a range of 250 to 500 nm (18, 31); however, the method is applicable to any other transparent layered structure of animal, plant, geologic, or synthetic origin.     

Adipokines and ghrelin in gastric cancer cachexia

AIM： To investigate the roles of the adipocytokines, ghrelin and leptin in gastric cancer cachexia.
METHODS： Resistin, ghrelin, leptin, adiponectin, insulin and insulin-like growth factor （IGF-Ⅰ）, were measured in 30 healthy subjects, and 60 gastric cancer patients of which 30 suffered from cancerinduced cachexia and 30 served as a control group. The relationships between hormones, body mass index （BMI） loss ratio, age, gender, and Glasgow Prognostic Score （GPS） were investigated.
RESULTS： Cachexia patients had higher tumor stage and GPS when compared with non-cachexia patients （P 〈 0.05）. Ghrelin, resistin, leptin, adiponectin and IGF- Ⅰ, showed a significant correlation with BMI loss ratio and GPS （P 〈 0.05）. A strong correlation was seen between GPS and BMI loss （R = -0.570, P 〈 0.0001）. Multivariate analysis indicated that BMI loss was significantly independent as a predictor of ghrelin, resistin, leptin and IGF-Ⅰ （P 〈 0.05）. Existence of an important significant relationship between resistin and insulin resistance was also noted.
CONCLUSION： These results showed that serum ghrelin, leptin, adiponectin, and IGF-Ⅰ play important roles in cachexia-related gastric cancers. No relationship was found between resistin and cancer cachexia. Also, because of the correlation between these parameters and GPS, these parameters might be used as a predictor factor.     

Fundoplication for gastroesophageal reflux disease: regional variability and factors predicting operative approach

We have recently shown that the majority of patients undergoing fundoplication in the United States are women. Based on these findings, we hypothesized that nonbiological factors contribute to the decisions on surgical reflux therapy. Using State Inpatient Databases of the Agency for Healthcare Research and Quality, we extracted annual fundoplication rates, sex distribution, age cohorts, racial background, and insurance coverage. To account for potential differences in state populations, the results were normalized and correlated with Census data, adult obesity rates, median income, poverty rates, and physician workforce within the state. Fundoplication rates varied fivefold between states, ranging from 4.1 ± 0.1 per 100 000 in New Jersey to 21.8 ± 0.4 per 100 000 in Oregon. Higher poverty rates and a higher fraction of Caucasians within a state independently predicted higher fundoplication rates. While the majority of operations were performed laparoscopically, surgical approaches also differed between states with rates of laparoscopic ranging from 52.3 ± 1.8% in Oklahoma to 87.4 ± 1.7% in Hawaii. A lower number of pediatric and Medicaid‐insured patient and a higher fraction of privately insured patients best predicted higher rates of laparoscopic surgery. Our study shows significant regional variation in surgical reflux management, which cannot be explained by differences in disease mechanisms. Insurance coverage and racial background influenced the likelihood of surgery, suggesting a role of financial incentives.     

Laparoscopic-assisted one-stage resection of rectal cancer with synchronous liver metastasis utilizing a pfannenstiel incision

Laparoscopic approaches have been increasingly used in selected patients with either colorectal or liver cancer. However, simultaneous resection of colorectal carcinoma with synchronous liver metastases is still a subject of debate. The present case describes combined laparoscopic rectal and liver resections for a patient with primary rectal cancer and a synchronous liver metastasis utilizing a Pfannenstiel incision for specimen extraction. The operative time was 370 min and estimated blood loss was 400 mL. Postoperatively, the patient required parenteral analgesia for 48 h, resumed normal diet on day 3 and was discharged on day 7 after the operation. A laparoscopic approach utilizing a Pfannenstiel extraction incision may present an advantageous and attractive option for simultaneous laparoscopic rectal and liver resection in selected patients with the aim of improving short-term outcomes.     

Serotonin transporter polyadenylation polymorphism modulates the retention of fear extinction memory

Growing evidence suggests serotonin's role in anxiety and depression is mediated by its effects on learned fear associations. Pharmacological and genetic manipulations of serotonin signaling in mice alter the retention of fear extinction learning, which is inversely associated with anxious temperament in mice and humans. Here, we test whether genetic variation in serotonin signaling in the form of a common human serotonin transporter polyadenylation polymorphism (STPP/rs3813034) is associated with spontaneous fear recovery after extinction. We show that the risk allele of this polymorphism is associated with impaired retention of fear extinction memory and heightened anxiety and depressive symptoms. These STPP associations in humans mirror the phenotypic effects of serotonin transporter knockout in mice, highlighting the STPP as a potential genetic locus underlying interindividual differences in serotonin transporter function in humans. Furthermore, we show that the serotonin transporter polyadenylation profile associated with the STPP risk allele is altered through the chronic administration of fluoxetine, a treatment that also facilitates retention of extinction learning. The propensity to form persistent fear associations due to poor extinction recall may be an intermediate phenotype mediating the effects of genetic variation in serotonergic function on anxiety and depression. The consistency and specificity of these data across species provide robust support for this hypothesis and suggest that the little-studied STPP may be an important risk factor for mood and anxiety disorders in humans.