Molecular Epidemic Characteristics and Genetic Evolution of Porcine Circovirus Type 2 (PCV2) in Swine Herds of Shanghai, China.

Porcine Circovirus 2 (PCV2) is a crucial swine pathogen and considered a primary causative agent of porcine circovirus-associated diseases (PCVADs), posing a serious economic threat to the swine industry across globe. The world's biggest agricultural conglomerates have teamed up to create giant commercial pig farms across Shanghai due to the proximity of this region to more affluent lean-pork markets. Since its discovery, PCV2 has displayed extraordinary genetic diversity, and its genome is swiftly evolving through a series of mutations and recombinations. However, limited information on epidemiology, molecular characteristics, vaccine cross-protection, and the co-infection rate of PCV2 with other lethal swine diseases can adversely impact the pig production in the region. To investigate the molecular epidemic characteristics and genetic evolution of PCV2, pigs with doubtful symptoms of PCVADs were sampled from various commercial pig farms with a history of PWMS and/or PDNS across Shanghai from 2014 to 2018. Our results revealed the coexistence of multiple PCV2 genotypes (PCV2b, PCV2e, and PCV2d) among Shanghai pig herds and dominance of PCV2d among them. We also found critical amino acid substitutions in epitope regions of important capsid proteins in PCV2 isolates involved in viral replication and host immune escape. Spotted mutations may favor the prevalence and survival of various PCV2 genotypes despite availability of commercial vaccines. This study also provides insight into the co-infection status of PCV2 with major lethal swine viral diseases such as PPV and PPRSV. Collectively, these investigations will contribute to understanding the molecular epidemiology and evolution of PCV2 across the region.

Epidemiological trends of foodborne Campylobacter outbreaks in the United States of America, 1998-2016.

Campylobacter is a major cause of foodborne diarrheal infections in the United States of America (USA). This study aimed to elucidate the patterns of Campylobacter foodborne outbreaks temporally and spatially concerning food vehicles. We collected the data of foodborne outbreaks from 1998 to 2016 reported to the Centers for Disease Control and Prevention. The incidence rate of outbreaks for each food source was calculated and analyzed for each variable including season, food location, and census region. Overall, 465 single-state outbreaks and 8003 cases were reported during 1998-2016. Outbreaks were frequently attributed to dairy products (32%), chicken (17%) and vegetables (6%). Binomial regression analysis showed that compared to chicken items, the highest rate ratio of outbreaks was associated with dairy products (1.86) followed by vegetables (1.35) and meat products (0.76). More outbreaks were reported in the summer (35%) followed by the spring (26%) and fall (22%) season. We found that the highest number of outbreaks occurred in the West 159 (34%) and Midwest 137 (29%) census regions. The study highlights the role of dairy, chicken, and vegetables as food vehicles in Campylobacter outbreaks. Findings from this study can help in devising strategies to mitigate the increasing occurrence of Campylobacter foodborne outbreaks.

Outbreaks of foodborne Salmonella enteritidis in the United States between 1990 and 2015: An analysis of epidemiological and spatial-temporal trends.

OBJECTIVES: To evaluate the role of eggs and other food vehicles as risk factors associated with Salmonella enteritidis (SE) outbreaks in order to address the endemicity of SE infections in the USA. METHODS: We retrieved and analyzed data relating to all SE outbreaks reported to the Centers for Disease Control and Prevention (CDC) between 1990 and 2015. We then used descriptive and analytical statistical methods, including negative binomial regression models for the estimation of rate-ratios, to analyze the data. RESULTS: Analyses showed that egg-based dishes were the most common food vehicle associated with outbreaks of SE in the USA (273 cases [24%]); this was followed by several other food items, including meat (130 cases [11%]), vegetables (96 cases [8%]), chicken items (95 cases [8%]), dairy products (55 cases [5%]), and bakery items (8 cases [1%]). Compared to egg-based dishes, other food items such as meat (exp(ß) = 0.51, 95% CI 0.37, 0.69), chicken (exp(ß) = 0.42, 95% CI 0.30, 0.58), vegetables (exp(ß) = 0.41, 95% CI 0.29, 0.55), and dairy items (exp(ß) = 0.27, 95% CI 0.18, 0.40) were significantly associated with outbreaks of SE in the USA. Of 1144 SE outbreaks, 402 (35%) occurred in the Northeast region of the USA, followed by the South (253 [22%]), West (250 [22%]), and Midwestern regions (239 [21%]). CONCLUSIONS: Epidemiological and spatiotemporal trends analyses demonstrated that a significant proportions of Salmonella enteritidis outbreaks in the USA are attributed to food vehicles other than eggs. Our findings can be used to plan effective strategies to mitigate the increasing occurrence of foodborne SE outbreaks.

Potential Role of Flavivirus NS2B-NS3 Proteases in Viral Pathogenesis and Anti-flavivirus Drug Discovery Employing Animal Cells and Models: A Review.

Flaviviruses are known to cause a variety of diseases in humans in different parts of the world. There are very limited numbers of antivirals to combat flavivirus infection, and therefore new drug targets must be explored. The flavivirus NS2B-NS3 proteases are responsible for the cleavage of the flavivirus polyprotein, which is necessary for productive viral infection and for causing clinical infections; therefore, they are a promising drug target for devising novel drugs against different flaviviruses. This review highlights the structural details of the NS2B-NS3 proteases of different flaviviruses, and also describes potential antiviral drugs that can interfere with the viral protease activity, as determined by various studies. Moreover, optimized in vitro reaction conditions for studying the NS2B-NS3 proteases of different flaviviruses may vary and have been incorporated in this review. The increasing availability of the in silico and crystallographic/structural details of flavivirus NS2B-NS3 proteases in free and drug-bound states can pave the path for the development of promising antiflavivirus drugs to be used in clinics. However, there is a paucity of information available on using animal cells and models for studying flavivirus NS2B-NS3 proteases, as well as on the testing of the antiviral drug efficacy against NS2B-NS3 proteases. Therefore, on the basis of recent studies, an effort has also been made to propose potential cellular and animal models for the study of flavivirus NS2B-NS3 proteases for the purposes of exploring flavivirus pathogenesis and for testing the efficacy of possible drugs targets, in vitro and in vivo.

Targeting nNOS ameliorates the severe neuropathic pain due to chronic pancreatitis.

BACKGROUND: Pain due to pancreatic cancer/PCa or chronic pancreatitis/CP, is notoriously resistant to the strongest pain medications. Here, we aimed at deciphering the specific molecular mediators of pain at surgical-stage pancreatic disease and to discover novel translational targets. METHODS: We performed a systematic, quantitative analysis of the neurotransmitter/neuroenzmye profile within intrapancreatic nerves of CP and PCa patients. Ex vivo neuronal cultures treated with human pancreatic extracts, conditional genetically engineered knockout mouse models of PCa and CP, and the cerulein-induced CP model were employed to explore the therapeutic potential of the identified targets. FINDINGS: We identified a unique enrichment of neuronal nitric-oxide-synthase (nNOS) in the pancreatic nerves of CP patients with increasing pain severity. Employment of ex vivo neuronal cultures treated with pancreatic tissue extracts of CP patients, and brain-derived-neurotrophic-factor-deficient (BDNF+/-) mice revealed neuronal enrichment of nNOS to be a consequence of BDNF loss in the progressively destroyed pancreatic tissue. Mechanistically, nNOS upregulation in sensory neurons was induced by tryptase secreted from perineural mast cells. In a head-to-head comparison of several genetically induced, painless mouse models of PCa (KPC, KC mice) or CP (Ptf1a-Cre;Atg5fl/fl) against the hypersecretion/cerulein-induced, painful CP mouse model, we show that a similar nNOS enrichment is present in the painful cerulein-CP model, but absent in painless genetic models. Consequently, mice afflicted with painful cerulein-induced CP could be significantly relieved upon treatment with the specific nNOS inhibitor NPLA. INTERPRETATION: We propose nNOS inhibition as a novel strategy to treat the unbearable pain in CP. FUND: Deutsche Forschungsgemeinschaft/DFG (DE2428/3-1 and 3-2).

Lipid nanoparticles with minimum burst release of TNF-α siRNA show strong activity against rheumatoid arthritis unresponsive to methotrexate.

TNF-α siRNA has shown promising therapeutic benefits in animal models of rheumatoid arthritis. However, there continues to be a need for siRNA delivery systems that have high siRNA encapsulation efficiency and minimum burst release of TNF-α siRNA, and can target inflamed tissues after intravenous administration. Herein we report a novel acid-sensitive sheddable PEGylated solid-lipid nanoparticle formulation of TNF-α-siRNA, AS-TNF-α-siRNA-SLNs, prepared by incorporating lipophilized TNF-α-siRNA into solid-lipid nanoparticles composed of biocompatible lipids such as lecithin and cholesterol. The nanoparticles are approximately 120 nm in diameter, have a high siRNA encapsulation efficiency (>90%) and a minimum burst release of siRNA (<5%), and increase the deilvery of the siRNA in chronic inflammation sites in mouse models, including in a mouse model with collagen-induced arthritis. Importantly, in a mouse model of collagen antibody-induced arthritis that does not respond to methotrexate therapy, intravenous injection of the AS-TNF-α-siRNA-SLNs significantly reduced paw thickness, bone loss, and histopathological scores. These findings highlight the potential of using this novel siRNA nanoparticle formulation to effectively treat arthritis, potentially in patients who do not respond adequately to methotrexate.

Wolbachia pipientis: A potential candidate for combating and eradicating dengue epidemics in Pakistan

Dengue virus syndrome is an emerging global health challenge which is endemic in tropical countries like Pakistan. In recent years dengue incidences have increased considerably in different areas of Pakistan with more sever impacts on urban and peri-urban populations. This review is an effort to highlight the changing epidemiology of dengue fever, role of Government of Pakistan in disease management and control using preventive and community based approaches in the region. Moreover, there is an emphasis on application of Wolbachia as novel, inexpensive and environmentally benign candidate for control and eradication of dengue transmitting vectors.

Wolbachia pipientis: A potential candidate for combating and eradicating dengue epidemics in Pakistan

Dengue virus syndrome is an emerging global health challenge which is endemic in tropical countries like Pakistan. In recent years dengue incidences have increased considerably in different areas of Pakistan with more sever impacts on urban and peri-urban populations. This review is an effort to highlight the changing epidemiology of dengue fever, role of Government of Pakistan in disease management and control using preventive and community based approaches in the region. Moreover, there is an emphasis on application of Wolbachia as novel, inexpensive and environmentally benign candidate for control and eradication of dengue transmitting vectors.

Clinical evaluation of coronally advanced flap with or without acellular dermal matrix graft on complete defect coverage for the treatment of multiple gingival recessions with thin tissue biotype.

AIM: The objective of this study was to compare acellular dermal matrix graft (ADM) combination with coronally advanced flap (CAF) on complete defect coverage, aesthetics and patient satisfaction with CAF alone for multiple recessions with gingival thickness (GT) <0.8 mm. MATERIALS AND METHODS: Forty-eight Miller Class I multiple recessions ≥3 mm were divided into test (CAF + ADM) and control (CAF) groups. At baseline and 12 months, recession height (RH), keratinized tissue height (KT), GT, mean and complete defect coverage were evaluated. Patient satisfaction, root coverage aesthetic score (RES) and the correlation between GT and defect coverage were also assessed. RESULTS: Baseline RH in CAF + ADM and CAF groups was 3.25 ± 0.34 mm and 3.21 ± 0.26 mm, respectively. Mean and complete defect coverage were 94.84% and 83.33% in test group, 74.99% and 50.00% in control group, respectively. Inter-group differences were found to be statistically significant for RH reduction, attachment gain, KT and GT increase, mean defect coverage and RES in favour of test group (p < 0.05). There was a significant positive correlation between GT and mean defect coverage (p < 0.05). CONCLUSION: Coronally advanced flap in association with ADM can be proposed as a valid approach for the treatment of multiple recessions with thin tissue biotype.

Electromagnetic wave scattering from a rough interface above a chiral medium: generalized field transforms.

In order to derive full-wave solutions for electromagnetic wave scattering from rough interfaces between achiral media (free space for instance) and chiral media that satisfy generalized constitutive relations, it is necessary to employ complete modal expansions for the electromagnetic fields above and below the interface. To this end, the familiar Fourier transforms of the fields are expressed as generalized field transforms consisting of the radiation term, the lateral waves, and the surface waves. Maxwell's equations are converted into generalized telegraphists' equations [in the companion paper (this issue), J. Opt. Soc. Am. A 30, 335 (2013)] upon the imposition of exact boundary conditions. These telegraphists' equations are coupled first-order differential equations for the forward- and backward-traveling wave amplitudes associated with all the different species of waves (radiation, lateral, and surface waves) excited at the surface of the chiral medium. The analysis presented here includes the completeness and orthogonal relations of the basis functions associated with the modal expansions. This work is used to distinguish between depolarization due to the chiral properties of the medium and depolarization due to surface irregularities. It has applications in remote sensing and identification of biological and chemical materials based on their optical activity.

Electromagnetic wave scattering from a rough interface above a chiral medium: generalized telegraphists' equations.

Using complete modal expansions for the electromagnetic fields above and below a rough interface between free space and chiral media and on imposing exact boundary conditions at the interface, Maxwell's equations are converted into generalized telegraphists' equations for the wave amplitudes of different species of waves (radiation far fields, lateral, and surface waves). The local basis functions, used in the complete modal expansions, are functions of the fluctuating surface height and medium parameters. The generalized telegraphists' equations are coupled first-order differential equations for the forward- and backward-traveling wave amplitudes. The coupling between the different species of waves is due to the fluctuations of the rough surface height and medium parameters. A Taylor series expansion of the surface element scattering matrix in terms of the chiral parameter is used to distinguish between depolarization due to surface roughness and the chiral properties of the medium. The analysis has applications in remote sensing and identification of biological and chemical materials through their optical activity.

Double-scatter cross sections for two-dimensional random rough surfaces that exhibit backscatter enhancement.

Full-wave solutions are given for the single- and double-scatter radar cross sections for two-dimensional random rough surfaces. High-frequency approximations are used for the double-scatter cross sections in order to express them as numerically tractable four-dimensional integrals. The major contributions to the double-scatter cross sections are associated with the quasi-parallel and quasi-antiparallel double-scatter paths. They come from the neighborhoods of specular points. The enhancement of the backscatter cross sections, which is associated with the quasi-antiparallel double-scatter paths, is observed for both the like- and cross-polarized cross sections.

Reagents for the chemical development of latent fingerprints: scope and limitations of benzo[f]ninhydrin in comparison to ninhydrin.

Benzo[f]ninhydrin was compared to ninhydrin for fingerprint development on paper. Overall, the performance of ninhydrin on exhibits was slightly better than that of benzo[f]ninhydrin. The significant advantages of the benzo[f]ninhydrin over ninhydrin were the much stronger fluorescence it gave after treatment with zinc salts and a slightly quicker reaction under ambient conditions. This fluorescence is, however, similar to that obtained with other reagents, such as DFO or ninhydrin analogs. These advantages apparently are not sufficient to justify regular usage of benzo[f]ninhydrin, especially when one considers its low solubility and high cost.

Scattering by layered structures with rough surfaces: comparison of polarimetric optical scatterometer measurements with theory.

A laboratory model of a layered structure with a rough upper surface (a glass microscope slide cut with a diamond saw) is used to obtain optical polarimetric data. Scatterometer measurements were made of all the Mueller matrix elements associated with light scattered in arbitrary directions. (A preliminary measurement of scattering from a smooth opaque gold film on a silicon wafer was used to validate the calculation of the Mueller matrix elements.) These measurements are compared with corresponding analytical solutions based on the full-wave approach. Physical interpretations of the analytical solutions that account for scattering upon reflection and transmission across rough interfaces are given in a companion paper. The agreement between calculations and measurements suggests that the full wave, polarimetric solutions can provide a reliable database for electromagnetic detection of rough surfaces in remote-sensing applications.

Computations of the Mueller matrix elements for scattering from layered structures with rough surfaces, with applications to optical detection.

A full-wave method is used to evaluate the Mueller matrix elements for scattering from layered structures with random rough surfaces. These provide a database for applications in optical detection over a broad range of rough surface statistical parameters. They can be used to determine the optimal frequencies and incident angles that provide most reliable measurements for optical detection. The elements of the Mueller matrix that are most sensitive to medium parameters of the layered structures can also be identified. Contributions from individual terms of the full-wave solutions are shown to have distinct physical interpretations.

Structural plasticity of optic synapses in the rat suprachiasmatic nucleus: adaptation to long-term influence of light and darkness.

Synapses of optic afferents (optic synapses) in the suprachiasmatic nucleus of hooded rats were morphometrically evaluated after exposing the animals to 12 h, 14 days, 2 months, and 8 months of constant light (light rats) and darkness (dark rats). Compared with dark rats, optic synapses from light rats have larger boutons with larger mitochondria, more clear vesicles, fewer dense-core vesicles and front-line vesicles, smaller presynaptic dense projections, a smaller amount of postsynaptic density material, a smaller relative number of Gray-type I (asymmetric) junctions, a greater relative number of Gray-type II (symmetric) junctions, as well as more and larger mitochondria in the postsynaptic dendrites. Junctions of optic synapses are mostly straight, but the small number of positively curved contacts are more flattened in light rats than in dark rats. An age-related increase in the size of presynaptic dense projections was also observed. There are no changes in the sizes of clear and dense-core vesicles, in the size of synaptic junctions and their numerical density in area, and in the unspecific contact area between pre- and postsynaptic elements. The changes in optic boutons are characteristic for activated and relatively disused synapses with a slow, tonic firing rate. It appears that (1) the amount of postsynaptic density material is proportional to the strength of Gray-type I synapses, and that (2) some excitatory optic synapses become inhibitory after long-term activity, whereas some inhibitory synapses turn into excitatory contacts after long-term disuse.

Recent trends in the incidence of lymphomas in Kuwait.

All cases of Hodgkin's disease (HD) and non-Hodgkin's lymphoma (NHL) reported to the Kuwait Cancer Registry between 1980-1989 were analyzed. Age specific and age standardized incidence rates were calculated for Kuwaiti and non-Kuwaiti males and females for the two periods of 1980-1984 and 1985-1989, and compared to detect short term changes. The study of 153 cases of HD and 325 cases of NHL in 1980-1984 and 213 cases of HD and 338 cases of NHL in 1985-1989 showed that HD incidence was stable in the two periods, the mixed cellularity subtype frequency and incidence declined, while the frequency and the incidence of nodular sclerosis increased significantly in the second period. These changes were most significant in the non-Kuwaiti males. The NHL incidence declined significantly in the 1985-1989 period. The incidence of low grade and intermediate grade NHL declined in the period of 1985-1989. The high grade NHL frequency increased, however, the annual incidence rate increase was not significant. The change in the HD subtypes may probably be related to the improvement in the socio-economic condition. The higher proportion of high grade lymphomas may be related to the population structure in Kuwait and is not related to the acquired immunodeficiency syndrome.

Febrile neutropenia in cancer patients in Kuwait: microbial spectrum and outcome.

A sample of 100 consecutive febrile neutropenic episodes in cancer patients in Kuwait was studied. Acute leukaemias (44%) and lymphomas (29%) were the most frequent underlying cancers; 21 bacteraemis (gram-positive 10, gram-negative 9, polymicrobial 2) were encountered. Staphylococcous epidermidis and Escherichia coli were the commonest organisms. Urinary tract infection occurred in 30% of the microbiologically documented cases. A total of 84 episodes responded to therapy and 9 of the 14 deaths were secondary to infection.

The epidemiology of leukemia in Kuwait.

This study reports the occurrence of leukemia subtypes in Kuwait between 1979 and 1989. The cases were analyzed by age, sex, Kuwaiti and non-Kuwaiti nationality status. Of the total 723 cases, acute lymphoblastic leukemia (ALL) was the most frequent (44.2%), exhibited a peak incidence in the 0-4 years age group and was also the most common leukemia of childhood (90.5%). Acute myeloblastic leukemia (AML) constituted 32.4% of leukemia and showed a progressive increase in incidence with age. Chronic myeloid leukemia (CML) constituted 14.8% and chronic lymphocytic leukemia (CLL) 8.6% of all cases. The incidence, age and sex distribution of ALL, AML and CML was similar to that in the developed Western countries while the lesser frequency of CLL was similar to that in the Orient. This pattern of leukemia subtypes may be related to the population structure consisting of the predominantly young in Kuwait, and the peak incidence of ALL in the very young to the socio-economic conditions.