To study the effect of dietary supplementation of lecithin and carnitine on growth performance and nutrient digestibility in pigs fed high-fat diet.A total of 30 weaned female large white Yorkshire piglets of 2 months of age were selected and randomly divided into three groups allotted to three dietary treatments, T1 - Control ration as per the National Research Council nutrient requirement, T2 - Control ration plus 5% fat, and T3 - T2 plus 0.5% lecithin plus 150 mg/kg carnitine. The total dry matter (DM) intake, fortnightly body weight of each individual animal was recorded. Digestibility trial was conducted toward the end of the experiment to determine the digestibility coefficient of various nutrients.There was a significant improvement (p<0.01) observed for pigs under supplementary groups T2 and T3 than that of control group (T1) with regards to growth parameters studied such as total DM intake, average final body weight and total weight gain whereas among supplementary groups, pigs reared on T3 group had better intake (p<0.01) when compared to T2 group. Statistical analysis of data revealed that no differences were observed (p>0.05) among the three treatments on average daily gain, feed conversion efficiency, and nutrient digestibility during the overall period.It was concluded that the dietary inclusion of animal fat at 5% level or animal fat along with lecithin (0.5%) and carnitine (150 mg/kg) improved the growth performance in pigs than non-supplemented group and from the economic point of view, dietary incorporation of animal fat at 5% would be beneficial for improving growth in pigs without dietary modifiers. Swine industry has a major economic impact on agriculture throughout the world. Compared to other livestock species, pig rearing is considered to be more advantageous due to its low investment for farming, quick returns, better feed conversion efficiency, higher fecundity, short generation interval, and significance in improving socioeconomic status of weaker section of the society ,2. Pork Feed cost plays a major role in determining profitability of swine production and feed itself contributes 65-75% of total cost of production . Cereal In swine diet, fat utilization can be improved by feed additives such as lecithin and L-carnitine. For proper utilization of fat by animals, they should be digested and absorbed well in gastrointestinal tract ,13. BecaAddition of higher quantities of fat in the diet for pigs may cause oxidative stress and to prevent this stress antioxidant such as vitamin E (α-tocopheryl acetate) is to be included in the diet. Antioxidants will protect fat from oxidation and thereby prevent the production of rancidity substances ,13. ConsThe experimental design and plan of this study strictly followed the norms of the Institutional Animal Ethics Committee of Kerala Veterinary and Animal Sciences University (KVASU), Pookode, Kerala. Requisite permission for the selection of animals and laboratory analysis was granted by Academic Council and Institutional Animal Ethics Committee of KVASU, Pookode, Kerala.The study was conducted at Centre for Pig Production and Research, College of Veterinary and Animal Sciences, Mannuthy, Thrissur.A total of 32 weaned female large white Yorkshire piglets of 2 months of age were selected and randomly divided into three dietary groups as uniformly as possible with regard to weight. Each group had four replicates with two piglets per replicate in control group (T1) and three piglets per replicate in experimental groups (T2 and T3). All piglets were maintained under uniform management conditions throughout the experimental period of 98 days. Each piglet was fed with standard grower and finisher ration containing 18% and 16% of crude protein (CP) and 3265 kcal of metabolizable energy per kg of feed. The three groups of piglets were allotted to three dietary treatments as follows: T1  intake. The piglets were weighed at the beginning of the experiment and subsequently at fortnightly intervals to estimate total weight gain, average daily gain, and feed conversion efficiency, respectively. A digestibility trial was conducted toward the end of the experiment to determine the digestibility coefficient of the nutrients and availability of minerals like calcium and phosphorus by total collection method.Chemical compositions of feed and fecal sample were analyzed as per methods described in Association of Official Analytical Chemists .Data collected on various parameters were statistically analyzed by completely randomized design method as described by Snedecor and Cochran . Means wst, 2nd and 12th week whereas supplementary groups (T2 and T3) showed similar and better intake than control group in all weekly intervals except 5th, 6th and 9th week where combination group (T3) showed higher intake than T1 and T2 group. This is in agreement with the findings of Overland and Sundstol [et al. [et al. [Data on weekly average feed intake of pigs given the three experimental rations T1, T2 and T3 are presented in Sundstol  and Piao [et al.  who had  [et al.  observedL-carnitine serves as a co-substrate for the enzyme carnitine acyltransferase for reversible acetylation of coenzyme A and thereby acts as a carrier for transport of long-chain fatty acid from the cytosol into the inner mitochondrial membrane for undergoing β-oxidation of fatty acids ,23. Carnet al. [et al. [Danek et al.  suggesteet al. ,21,29 re [et al.  revealed [et al. . For ass [et al. ,32.et al. [et al. [et al. [et al. [et al. [The data with regard to fortnightly average body weight of pigs are presented in et al.  and Brumet al.  who had  [et al.  observed [et al.  had repo [et al.  reported [et al.  reported [et al.  reportedet al. [et al. [et al. [et al. [et al. [et al. [Statistical analysis of data presented in et al.  who had  [et al.  had obse [et al.  had repo [et al.  inferred [et al.  observed [et al.  by supplet al. [et al. [The apparent digestibility of nutrients and availability of minerals in the experimental rations estimated from digestibility trial in pigs belonging to three dietary treatments are represented graphically in Figures-et al.  reported [et al.  noticed The cost of feed per kg for three rations  for the overall period was Rs. 24.38, 25.41 and 27.56, respectively. The cost of ingredients used for this study was as per the rate contract fixed for the supply of various feed ingredients to the farm for the year 2014-2015. The cost of feed per kg body weight gain of pigs maintained on the three dietary treatments was Rs. 77.37, 75.03 and 80.00 for the overall period and the values were statistically similar.The dietary incorporation of animal fat at 5% level or animal fat along with lecithin (0.5%) and carnitine (150 mg/kg) had significantly improved the total DM intake, average final body weight, and total weight gain in pigs than non-supplemented group but no differences were observed among them for average daily gain, feed conversion efficiency, and nutrient digestibility during the overall period. From the economic point of view, dietary supplementation of animal fat at five per cent level (T2) would be beneficial for improving the growth in weaned Large White Yorkshire pigs without dietary modifiers.KA was involved in the design of the study. AS carried out the experiment, collection, and analysis of the data and prepared the first draft of the manuscript under the guidance of KA. KA, PG revised the manuscript. PSB drafted and edited the manuscript.


Gallus gallus, at least 8 maternal lineages have been identified. While breeds distributed westward from the Indian subcontinent usually share haplotypes from 1 to 2 haplogroups, Southeast Asian breeds exhibit all the haplogroups. The Vietnamese Ha Giang (HG) chicken has been shown to exhibit a very high nuclear diversity but also important rates of admixture with wild relatives. Its geographical position, within one of the chicken domestication centres ranging from Thailand to the Chinese Yunnan province, increases the probability of observing a very high genetic diversity for maternal lineages, and in a way, improving our understanding of the chicken domestication process.Chickens represent an important animal genetic resource and the conservation of local breeds is an issue for the preservation of this resource. The genetic diversity of a breed is mainly evaluated through its nuclear diversity. However, nuclear genetic diversity does not provide the same information as mitochondrial genetic diversity. For the species A total of 106 sequences from Vietnamese HG chickens were first compared to the sequences of published Chinese breeds. The 25 haplotypes observed in the Vietnamese HG population belonged to six previously published haplogroups which are: A, B, C, D, F and G. On average, breeds from the Chinese Yunnan province carried haplotypes from 4.3 haplogroups. For the HG population, haplogroup diversity is found at both the province and the village level (0.69).G. gallus spadiceus. However, there was no geographical evidence of gene flow between wild and domestic populations as observed when microsatellites were used.The AMOVA results show that genetic diversity occurred within the breeds rather than between breeds or provinces. Regarding the global structure of the mtDNA diversity per population, a characteristic of the HG population was the occurrence of similar pattern distribution as compared to In contrast to other chicken populations, the HG chicken population showed very high genetic diversity at both the nuclear and mitochondrial levels. Due to its past and recent history, this population accumulates a specific and rich gene pool highlighting its interest and the need for conservation. Gallus gallus gallus is the primary maternal ancestor of the domestic chicken  and one in the Indian subcontinent. Furthermore, in a recent study, Errikson et al. [G. sonneratii).Chickens represent an important protein source for humans, as shown by a strong increase of poultry production around the world . Local populations contribute more specifically, to family poultry production, which is quite important for low income farmers from Africa, Asia, Latin America and the South Pacific. These local populations that are easy to raise, are resilient to harsh environmental conditions and may harbour original features of disease resistance . Within esticus; ). Liu et [et al.  showed tn et al.  highlighet al. [Liu et al.  performeet al. ,9,10. Soet al. ,11. In Let al. ,13. In Aet al. . The hetOn the basis of microsatellite information, African and Asian local chicken populations showed high genetic diversity ,5,4,11. In a previous analysis, we demonstrated that the local population of Vietnamese chickens, namely the H'mong chicken, showed a high genetic diversity and could not be subdivided into subpopulations . This poet al. [et al. [G. g. gallus  and one population of G. g. spadiceus from Thailand (Gg1). Thus, a total of 30 new sequences of Red junglefowl were added.Vietnamese chickens originate from the northern Ha Giang province  bordering the Yunnan Chinese province. The local chicken population from this province was previously considered to belong to the H'mong Black skin chicken. However previous genetic data demonstrated that no breed differentiation and no congruence between the black phenotype and the genetic structure occurred in the province . Therefoet al. , chicken [et al. : two popet al. [et al. [Details on chicken blood collection and DNA extraction were described previously in Berthouly et al. . Laws an [et al. . PCR proGallus gallus, involving 4 subspecies  and 437 Gallus gallus domesticus (40 Chinese breeds) already analysed by Liu et al. [HM462082-HM462217).Vietnamese samples were compared with 93 wild u et al. . The seqet al. [h) diversity, nucleotide (π) diversity, pairwise differences, and a Minimum Spanning Tree (MST) from Kimura-2 parameter distances  betweenes , analyset al. [et al. [G. gallus murghi, with sequences from Sri Lanka chickens published by Silva et al. [et al. [In order to have a more general view of the distribution of chicken haplogroups, we combined our data with haplotypes published by Oka et al.  on Japan [et al.  on Indiaa et al.  and with [et al. . We used [et al. ) to esti [et al. . Applyin [et al.  and the et al. [Gallus gallus from Hanoï, H  and E  [For the HG chicken population, we obtained a segment of 506 bp of mtDNA HVS-I sequence. Among the 106 sequences, 33 variables sites were found, involving 36 mutational events, which defined 25 haplotypes. All but 6 mutations were transitions. The 25 haplotypes observed belonged to six haplogroups previously found by Liu et al.  which ar Africa) ,11-13. TG. g. gallus Gg3 population from Vietnam, 2 haplotypes, G6 and G25 were observed. This corroborates the result from Liu et al. [G. gallus gallus population (i.e. Gg2). Haplotypes from clade A were not observed in such a population in previous published studies. In both populations from Thailand, Gg1 and Gg2, we found three new haplotypes from clade I. Until now, this clade was only represented by 2 haplotypes in samples originating from Vietnam [From our u et al. , who onl Vietnam . Thus, c(h) and nucleotide diversity (π) per commune ranged from 0.75 to 1 (mean h = 0.86 ± 0.088) and from 0.007 to 0.019 (mean π = 0.013 ± 0.004) respectively (Table π = 0.013 ± 0.005).In the HG population, haplotype diversity ly Table . The higet al. [As aforementioned, six haplogroups where found in the HG province. Only the Chinese Lv'erwu breed exhibited a similar rate. On average, breeds from the Yunnan province carried haplotypes from 4.3 haplogroups. With the HG population, this haplogroup diversity was not only found at the province level, but also at the village level. For villages where at least three animals were sampled, haplotype diversity averaged 0.86 and haplogroup diversity 0.69. This means that within a village, nearly two chickens out of three carried sequences from two different matriarchal haplogroups. This is extremely high and implies that conserving chickens from only one village from the HG province would make it possible to maintain more matriarchal lineages than would the conservation of African, Chilean or Indian local chickens ,13,14. Tet al. . This poet al. . Poolinget al. . These rK2P distance. This analysis excluded the four breeds that carried only one haplotype. The K2P plot . When the breeds were grouped according to geographic location (provinces), the major part of diversity was present within breeds 80.2%), while only a fraction was diagnostic of the provinces (4.8%). The remaining variation was present between breeds within each of the provinces (14%). Multidimensional scaling was constructed using %, while 2 test; P = 0.251). In other words, no geographic distribution pattern of haplogroups was observed in the Ha Giang province. This result, in agreement with nuclear data [Commune average pairwise differences were only significant for three pairwise commune comparisons: communes 65 and 40; communes 65 and 20; and communes 88 and 7. Two major haplotypes B1 and A1 occurred at frequencies 33% and 11% respectively overall in the HG population ..G. gallu2 test; P = 0.451) between admixed vs. non-admixed were observed. Even if some farmers admit catching eggs in the forest of these admixed communes, the occurrence of such a practice may be lower than hybridisation between wild cocks and domestic hens. This implies that hybrid offspring of crosses between domestic cocks and junglefowl hens are uncommon or rarely back-crossed into the domestic population while the hybrid offspring of domestic females and wild males could be more easily integrated into the domestic population. Thus, such communes can not be discriminated using mtDNA but they can be discriminated with the use of microsatellites which take into account male as well as female mediated gene flows. Examination of wild sympatric populations from the Ha Giang province would be necessary to ascertain the presence or absence of mtDNA gene flow from wild to domestic populations.In a previous analysis of nuclear diversity , four coet al.  and Silva et al.  this haplogroup belongs to an ancestral population from the Indian subcontinent that is now extinct. Furthermore, Haplogroup C has mainly been found in Japanese breeds that originate from commercial exchanges with Korea, Taiwan or the eastern provinces of China [We combined all sequences published by Oka et al. (; Japanes[et al. (; Indian  et al. (; Sri Lan([et al. . We foun [et al. , we founs Figure . An impou et al. . Moreoveu et al. , 45% of  [et al. . Haplogr [et al. . Assumin. murghi , but onl. gallus . Therefoof China . This haThe Vietnamese HG chicken showed high genetic diversity at both the nuclear and the mitochondrial level when compared to other local breeds. This genetic diversity is the result of many factors. One of the most important is the geographical position within a domestication centre area. Furthermore, we should not underestimate the impact of human and livestock migrations. This genetic diversity has been moreover supplied by the continuous current gene flow between domestic and wild population as shown with nuclear DNA . Hence, et al. [et al. [However, the widespread occurrence of free-ranging livestock is raising fear that introgressive hybridisation with wild populations would lead to a loss of biodiversity in the wild populations that could decrease their fitness. Chazara et al.  suggeste [et al.  showed tAll authors read and approved the final manuscript. NVT carried out sample collection; CB carried out sample collection, sequencing, the computational analysis and prepared the manuscript; GM created the distribution maps, XR and JRM participated in the computational analysis and preparation of the manuscript; BB and NB participated in the sequencing, MTB contributed to the revision of the manuscript; EV participated in the design of the study and the revision of the manuscript; VCC participated in the coordination of the study; JCM participated in the design, coordination of the study, and revision of the manuscript.DOC Samples information. Summary of breeds used, their origin, number of individuals and GenBank accession numbers.Click here for file


Littoral cell angioma is a rare primary vascular neoplasm of the spleen, composed of littoral cells that line the splenic sinuses of the red pulp. It was thought to be a benign, incidental lesion. However, many recent reports have described it to be a malignant lesion with congenital and immunological associations. The definitive diagnosis can only be made after histology and immunohistochemistry studies. She had been diagnosed with a thyroid adenoma with cystic degeneration 20 years ago and had persistent complaints of fatigue for the last 2 years. On physical examination, she was found to have hepatosplenomegaly. Blood examination showed moderate anemia; liver and renal function tests were normal. CT scan and MRI were performed. No splenic mass was seen on nonenhanced CT;  however,A 47-year-old Chinese male was found to have multiple splenic lesions. On B-mode USG, hemangioma was suspected and CT scan showed multiple lesions of the spleen . The patet al.[13et al.[34LCA is usually asymptomatic >55%) and is only discovered incidentally. It has no predilection for any particular age-group or sex; cases have been reported over the age range of 1–77 years (median age: 50 years) and in both sexes 5. Howeve5% and iset al. females et al.1 Recent ret al.134 Associet al.13 Bi et al3et al.348On unenhanced CT scan, LCA masses are only rarely visible ; however49In conclusion, LCA, is a rare vascular benign tumor of the spleen that may portend malignancy–4 and ma


Human enteric viruses are causative agents in both developed and developing countries of many non-bacterial gastrointestinal tract infections, respiratory tract infections, conjunctivitis, hepatitis and other more serious infections with high morbidity and mortality in immunocompromised individuals such as meningitis, encephalitis and paralysis. Human enteric viruses infect and replicate in the gastrointestinal tract of their hosts and are released in large quantities in the stools of infected individuals. The discharge of inadequately treated sewage effluents is the most common source of enteric viral pathogens in aquatic environments. Due to the lack of correlation between the inactivation rates of bacterial indicators and viral pathogens, human adenoviruses have been proposed as a suitable index for the effective indication of viral contaminants in aquatic environments. This paper reviews the major genera of pathogenic human enteric viruses, their pathogenicity and epidemiology, as well as the role of wastewater effluents in their transmission. Patients suffering from viral gastroenteritis or viral hepatitis may excrete about 10of stool . Consequof stool .Human enteric viruses are causative agents of many non-bacterial gastrointestinal tract infections, respiratory infections, conjunctivitis, hepatitis and other serious infections such as meningitis, encephalitis and paralysis. These are common in immunocompromised individuals with high morbidity and mortality attributable to these infections in both developed and developing countries. Most cases of enteric virus infections have particularly been observed to originate from contaminated drinking water sources, recreational waters and foods contaminated by sewage and sewage effluents waters .Wastewater treatment processes such as the activated sludge process, oxidation ponds, activated carbon treatment, filtration, and lime coagulation and chlorination only eliminate between 50% and 90% of viruses present in wastewater , the use2.A diverse range of enteric virus genera and species colonize the gastrointestinal tracts of humans producing a range of clinical manifestations and varying epidemiological features. From a public health perspective, the most important of these are the rotaviruses, adenoviruses, noroviruses, enteroviruses as well as Hepatitis A and E viruses.2.1.Rotaviruses are large 70 nm nonenveloped icosahedral viruses that belong to the family Reoviridae . A rotavThere are seven species of rotaviruses, designated A to G, of which groups A–C infect humans . At leasN-acetylneuraminic  acid residues on the cell surface membrane of the host cell, followed by VP5* or directly by VP5* without the involvement of sialic acid residues. In both cases, the identity of the receptors has remained unclear although, they are thought to be part of lipid micro domains [Rotaviruses infect mature enterocytes in the mid and upper villous epithelium of the host’s small intestines . During  domains . As a re domains . After c domains .+ ions, results in the transit of undigested mono- and disaccharides, fats, and proteins into the colon. The undigested bolus is osmotically active, resulting in impairment water absorption by the colon which leads to an osmotic diarrhea [The pathology of rotavirus infections have been based on a few studies of the jejunal mucosa of infected infants which have revealed shortening and atrophy of villi, distended endoplasmic reticulum, mononuclear cell infiltration, mitochondrial swelling and denudation of microvilli . Rotavirdiarrhea . The cladiarrhea . Severe diarrhea .Rotaviruses have been recognized as the leading cause of severe diarrhea in children below 5 years of age, with an estimated 140 million cases and about 800,000 deaths and about 25% of all diarrheal hospital admissions in developing countries each year . Group A2.2.Human enteroviruses are members of the family Picornaviridae, which consist of nonenveloped virus particles containing a 7,500-nucleotide single-stranded positive sense RNA genome protected by an icosahedral capsid . The genα2β1, αvβ3, and αvβ6), decay-accelerating factor , the coxsackievirus-adenovirus receptor (CAR), and intracellular adhesion molecule 1 (ICAM-1) [The pathogenicity of enteroviruses is mediated by an arginine-glycine-aspartic acid (RGD) motif found on the viral capsid proteins of the picornavirus family . About s(ICAM-1) . Typical(ICAM-1) .Most enterovirus infections are asymptomatic or result in only mild illnesses, such as non-specific febrile illness or mild upper respiratory tract infections. However, enteroviruses can also cause a wide variety of clinical illnesses including acute haemorrhagic conjunctivitis, aseptic meningitis, undifferentiated rash, acute flaccid paralysis, myocarditis and neonatal sepsis-like disease . EnterovOne of the most distinctive enterovirus diseases is poliomyelitis. It is almost invariably caused by one of the three poliovirus serotypes. Polioviruses may also cause aseptic meningitis or nonspecific minor illness . The nor2.3.Adenoviruses are nonenveloped viruses, about 90 nm in diameter with a linear, double-stranded DNA genome of 34–48 kb and an icosahedral capsid . On the vβ3 or αvβ5 integrins leading to endocytosis [Adenovirus infection of host epithelial  cells is mediated by the fibre and penton base capsid proteins. In the case of adenovirus subgroups A and C–F, the attachment to cells is mediated by a high affinity binding of the fiber protein to a 46 kDa membrane protein known as the coxsackie adenovirus receptor (CAR), a member of the immunoglobulin receptor super family serving as a cell to cell adhesion molecule in tight junctions . Subgrouocytosis .The major receptor for adenoviruses, CAR is not normally accessible from the apical surfaces. As a result, the initial adenovirus infection is presumed to occur through transient breaks in the epithelium allowing the luminal virus to reach its receptor or during the repair of injured epithelium when CAR might be accessible . FollowiAdenovirus infections occur worldwide throughout the year . The ser2.4.Noroviruses are members of the family Caliciviridae . NorovirThe VP1 subunit consists of a shell (S) and a protruding (P) domain that is made up of a middle P1 and a distal P2 subdomains . While tNoroviruses are a major cause of acute viral gastroenteritis, affecting people of all age groups worldwide . Outbrea3.Municipal wastewater is a mixture of human excreta (sewage), suspended solids, debris and a variety of chemicals that originate from residential, commercial and industrial activities . Raw sewThe assessment of the microbiological quality of wastewater effluents has traditionally depended on indicator organisms, such as coliforms or enterococci, which however do not always reflect the risk of other microbial pathogens such as viruses, stressed bacterial pathogens and protozoa . In partViral pathogens have frequently been detected in waters that comply with bacterial standards ,62. Huma4.Enteric viruses in wastewater treatment plants are removed by a combination of irreversible adsorption as well as inactivation by disinfectants . ProcessThe inactivation of viruses by disinfection is a process affected by suspended particles. Disinfection relies on the ability of either chemical disinfectant molecules or high-energy photons (in the case of UV disinfection) coming into contact with the viruses . Chemica5.et al. [Escherichia coli and Enterococcus faecalis were rapidly inactivated by chlorine with inactivation levels of (>5 log10 units) while there was poor inactivation (0.2 to 1.0 log10 unit) of F+-specific RNA (FRNA) bacteriophage (MS2) at doses of 8, 16, and 30 mg/liter of free chlorine. Armon et al. [The study of the inactivation of enteric viruses following wastewater disinfection is complicated by the low and variable levels of enteric viruses frequently seen in effluents . Researcet al. , observen et al.  also shon et al. .Ct values, defined as disinfectant concentration (C) multiplied by the contact time (t) between the disinfectant and microorganism. The recommendations direct that public utilities must ensure a 4-log (Ct 99.99%) inactivation of viruses [In the United States, the Environmental Protection Agency (EPA) recommends the use of an additional criterion for the evaluation of water disinfection based on viral inactivation. The standard makes use of  viruses .6.−3 to 1.0 × 102 liter−1 depending on the level of treatment [et al. [The inability of wastewater treatment systems to ensure a complete inactivation of viruses in wastewater effluents has serious implications on public health. Virus levels in treated wastewater, measured by cell culture assay, range from 1.0 × 10reatment . Human e [et al.  detected [et al. . Even hi [et al. .7.The discharge of inadequately treated sewage water has a direct impact on the microbiological quality of surface waters and consequently the potable water derived from it. The inherent resistance of enteric viruses to water disinfection processes means that they may likely be present in drinking water exposing consumers to the likelihood of infection. In one study, Human adenoviruses were detected in about 22% of river water samples and about 6% of treated water samples in South Africa . In anotEnteric viruses are the most likely human pathogens to contaminate groundwater. Their extremely small size, allows them to infiltrate soils from contamination sources such as broken sewage pipes and septic tanks, eventually reaching aquifers. Viruses can move considerable distances in the subsurface environment with penetration as great as 67 m and horizontal migration as far as 408 m . In a stet al. [3 virus particles·liter−1 in recreational beaches in America. Mocé-Llivina et al. [Another important human exposure pathway is through recreational waters. Human enteric viruses have frequently been detected in coastal waters receiving treated wastewater effluents. Xagoraraki et al.  reporteda et al.  detecteda et al. .et al. [et al. [Numerous outbreaks of enteric virus associated diarrhea have been linked to the consumption of water contaminated with viruses. Kukkula et al. , showed  [et al.  reported8.et al. [et al. [Viral contaminants may persist on food surfaces or within foods for extended periods . Pre-haret al.  showed a [et al.  using seet al. [Post-harvest contamination of raw food may occur as a result of human handling by workers and consumers, contaminated harvesting equipment, transport containers, contaminated aerosols, wash and rinse water or cross contamination during transportation and storage . Recontaet al.  using seet al. .et al. [Probably one of the most recognized food borne transmission of enteric virus infections is through the consumption of shellfish grown in sewage polluted marine environments. Shellfish, which includes molluscs such as oysters, mussels, cockles, clams and crustaceans such as crabs, shrimps, and prawns , are filet al.  report met al. –100 was et al. . Althouget al. .9.Current safety standards for determining food and water quality typically do not specify what level of viruses should be considered acceptable. This is in spite of the fact that viruses are generally more stable than common bacterial indicators in the environment. While there has been a significant amount of research on the impacts of inadequately treated wastewater effluents in developed countries, the same can not be said of developing countries which coincidentally are faced with a huge burden of infectious diseases emanating from pollution of water bodies with wastewater effluent discharges (von Sperling and Chernicharo  most of et al. [The challenge in ensuring safe water with regards to viral pathogens is that the detection of putative indicators of viral pathogens such as bacteriophages does not always correlate with that of other viruses particularly pathogenic enteric viruses . Human aet al. , adenoviet al. . Adenoviet al. , suggestet al. . To thiset al. , polyomaet al.  which shet al. . The impet al. , and thaet al. .


Although there has been more than 100 years since Miller first postulated about the caries etiopathogenesis, this disease remains the most prevalent noncontagious infectious disease in humans. It is clear that the current approaches to decrease the prevalence of caries in human populations, including water fluoridation and school-based programs, are not enough to protect everyone. The US National Institutes of Health Consensus Development Program released a statement in 2001 entitled “Diagnosis and Management of Dental Caries Throughout Life: : 1–24) and listed six major clinical caries research directions. The “epidemiology of primary and secondary caries” needs to be systematically studied with population cohort studies that collect information on natural history, treatment, and outcomes across the age spectrum.Research into “diagnostic methods”, including established and new devices and techniques, is needed. Development of standardized methods of calibrating examiners is also needed.“Clinical trials” of established and new treatment methods are needed. These should conform to contemporary standards of design, implementation, analysis, and reporting. They should include trials of efficacy.Systematic research on caries “risk assessment” is needed using population-based cohort techniques.Studies of “clinical practice” including effectiveness, quality of care, outcomes, health-related quality of life, and appropriateness of care are needed.“Genetic” studies are necessary to identify genes and genetic markers of diagnostic, prognostic, and therapeutic value.This Special Issue is a sample of the current research efforts addressing a subset of the topics described above. I would like to thank the authors for their excellent contributions, in addition to many colleagues who assisted me in the peer-review process. Finally, I would like to thank the support provided by my Guest Editors, Dr. Marilia Buzalaf, from the University of São Paulo, Brazil, and Dr. Figen Seymen, from the Istanbul University, Turkey.On the topic of “epidemiology and caries risk assessment” F. J. S. Pieralisi et al., K. K. Mäkinen, J. Vanobbergen et al., M. Okada et al., M. Ferraro and A. K. Vieira, A. P. Dasanayake et al., and J. D. Ruby et al. provide different perspectives to the problem which are good examples of how difficult is to study this multifaceted disease in a more comprehensive fashion.There is currently great interest in “diagnostic methods,” and the use of technology to differentiate diseased and healthy tissue, as well as to provide care. Different aspects of diagnostic and treatment approaches are addressed by S. Umemori et al., M. Aspiras et al., J. Wu et al., L. Karlsson, M. Yildirim et al., and A. Huminicki et al.The biggest challenge continues to be designing rigorous clinical trials that can provide conclusive answers related to approaches that more effectively control caries at the segments of the population with higher risk for developing the disease.I invite you to read, evaluate, and share this collection of 13 papers that comprise this special issue. Furthermore, I hope the readers will be interested in participating more actively in this debate of what approaches are more efficient to revert the current figures of caries prevalence and what aspects of this disease should be the focus of research in the coming years.Alexandre R. VieiraAlexandre R. Vieira


Sir,et al. with great interest.[et al. concluded that this observation was due to neonatal adrenal hemorrhage.[I read the recent publication on neonatal adrenal hemorrhage by Qureshi interest. The authinterest. Qureshi morrhage. There mimorrhage.


Although irritable bowel syndrome (IBS) is a common gastrointestinal disorder, its prevalence is unknown, especially in the urban population of Bangladesh. This community-based study aimed to find out the prevalence of IBS and healthcare-seeking patterns using the Rome-II definition.P ≤ 0.05.A population-based cross-sectional survey of 1503 persons aged 15 years and above was carried out in an urban community of Bangladesh. The subjects were interviewed using a valid questionnaire based on Rome-II criteria in a home setting. Statistical analysis was performed with Statistical Package for Social Science (SPSS) Programmers and the level of significance was set at n = 116) with a male to female ratio of 1:1.36 (49 vs. 67). “Diarrhoea-predominant IBS”  was the predominant IBS subgroup. Symptoms of abdominal pain associated with a change in stool frequency (100%) and consistency (88.8%) were quite common. All IBS symptoms were more prevalent among women (P < 0.000). In the past one year, 65.5% (n = 76) IBS subjects had consulted a physician with a slightly higher rate of women consulters (68.6 vs. 61.2%). The main predictor for healthcare-seeking was the presence of multiple dyspeptic symptoms.A response rate of 97.2% yielded 1503 questionnaires for analysis. The prevalence of IBS was found to be 7.7% (The prevalence of IBS in the urban community was found to be similar to that in rural communities. A higher rate of consultation was found among urban IBS subjects than in the rural subjects, with sex not seen to be a discriminator to seek consultation. The overall prevalence rates of irritable bowel syndrome (IBS) are similar 10-20%) in most industrialized countries.0-20% in  Limited Only 10-56% of adults with symptoms of IBS present for medical evaluation.1017 This10The present study aimed to find out the overall prevalence of IBS and healthcare-seeking patterns in an urban community of Bangladesh using the Rome-II definition. One of the purposes of this study was to arrive at a diagnosis without the help of investigations.This observational study was conducted from the months of November 2004 to March 2005. A valid questionnaire was administered using home-based personal interviews to 1503 subjects aged 15 years and above in a defined area of Dhaka city of Bangladesh. Door-to-door surveys were carried out by physicians assisted by community healthcare workers.The questionnaire was based on a previously published study conducteNo laboratory tests or endoscopic examinations were done in the study due to lack of feasibility.For this study, “Rome-II” definition of IBS required abdominal pain and at least two or more of the three abdominal pain symptoms  occurrinP ≤ 0.05.The data were processed for handling, and statistical analysis was performed with the computer-based Statistical Package for Social Science (SPSS) Programmers. Significance values were assessed during comparisons using the Chi-squared test with Yates' correction whenever necessary, and the level of significance was set at n = 116) using the Rome-II study definition. The gender-specific prevalence was 8.6 cases per 100 (n = 67) in women, and 6.7 cases per 100 (n = 49) in men. IBS was 1.36 times more prevalent in females than in males (P > 0.05). The majority  of the IBS cases were in the 15–44 years' age group [The mean age of the study population was 32.18±12.98 years with an age range of 15 to 97 years. The crude age- and gender-specific prevalence estimates and the prevalence of IBS subgroups have been described in ge group . No otheIBS subgroups summarized in n = 116) and consistency  was quite common in the urban community. Colonic pain tended to be spastic in nature, i.e., the pain was relieved by defecation in 37.0% (n = 43) of the IBS cases. All IBS symptoms were more prevalent in women than in men and these differences were statistically significant (P < 0.000).The symptom responses of subjects summarized in P < 0.000).The majority  of the IBS subjects reported having dyspeptic symptoms with heartburn in 84, of which were 30.17% were male and 42.24% were female. Frequent belching was seen in 78 , nocturnal abdominal pain was seen in 38 (32.7%), and vomiting was seen in nine (7.7%) cases. All the dyspeptic symptoms like heartburn and frequent belching were found in higher frequency in females; these differences were statistically significant (P >0.05). The consultation rate was found to increase with increasing age (P = 0.002) with heartburn and frequent belching being the two most common causes for consultation [P = 0.031). The main predictor for seeking healthcare was the presence of multiple dyspeptic symptoms. Only nine (7.7%) IBS subjects consulted healthcare professionals for the severity of their symptoms.Approximately 76 (65.51%) IBS subjects consulted a physician in the past one year with a higher rate of women consulters  cases in this survey [et al.[et al.[et al.[Abdominal pain associated with a change in stool frequency and/or consistency was present in all the IBS  was the predominant IBS subgroup (50%) in the urban survey, only 0.8% cases had diarrhea-predominant IBS in the rural survey.[et al, reported almost equal prevalence of diarrhea-predominant and constipation-predominant IBS in a Canadian population according to Rome-II criteria.[et al.[et al.[et al.[Whereas “diarrhea-predominant IBS” n = 5 was the criteria. All the a.[et al. reportedl.[et al.n = 76) had consulted a physician in the past one year, and there was a slightly higher rate of women consulters (68.6 vs. 61.2%). These findings are consistent with those of Heaton et al.[et al.[et al.[et al.[et al.[et al.[n = 62; 81.57%) of IBS subjects were found to consult for multiple symptoms in this study. Masud et al.[et al.[et al.[et al.[et al.[The majority of IBS subjects (on et al. and Jonel.[et al. Talley el.[et al. however,l.[et al. but not l.[et al. The majoud et al. the datal.[et al. No signil.[et al.; the nexl.[et al. reportedl.[et al. reportedThis study demonstrated that the prevalence of IBS in the urban population of Bangladesh was similar to that reported by most other recent population-based studies done in other countries and also to that of the rural population when compared on the basis of strict Rome-II criteria. From the findings of the present study, we can conclude that IBS prevalence does not seem to be confounded by the factors which are likely to differ between western and non-western lifestyles, or between urban and rural lifestyles. A good number of IBS subjects seek healthcare for their dyspeptic symptoms with increasing age, and the numbers of dyspeptic symptoms were found to be important discriminators to seek consultation. We still have a poor understanding of the triggers for consultation among these patients. More research is required and preferably with psycho-social assessment and some appropriate investigations to find out the exact prevalence of IBS in urban people and to clarify patients' reasons for seeking medical advice.


Sir,et al. studied on eight cases with mumps-induced orchitis and concluded that “long-term follow-up is recommended for all patients with abnormal semen analysis, particularly those with bilateral testicular involvement, since they may develop oligoasthenospermia several years after the infection or improve with item”.[Infection is accepted as a possible underlying cause of male infertility. Some infections are confirmed for the negative effect on sperm quality, for example, genital tract infection. In additth item”. However,et al. reported that a febrile episode could have marked effects on semen parameters and sperm DNA integrity and this might be related to future infertility.[et al. studied the characteristics of human sperm chromatin structure following an episode of influenza and high fever and found that influenza could have latent effects on sperm chromatin structure and might result in transient release of abnormal sperm.[et al. studied in a mice model and reported that human influenza virus could induce chromosome aberration of spermatozoa.[The influenza is a respiratory virus infection. It mainly affects the respiratory tract. However, there are some reports on the effect of influenza on sperm quality. As a febrile illness, influenza might affect the semen quality. Sergerie ertility. Evenson al sperm. Indeed, rmatozoa. Thadani rmatozoa.8 Sharma rmatozoa. These arrmatozoa.et al.[Hence, it can be concluded that there are strong evidences confirming the effect of influenza infection on sperm quality. The query if influenza can induce future infertility is interesting. There is a lack of evidence on this topic. Indeed, there are some reports confirming that influenza might lead to infertility in animals but not in human beings. However,et al. this miget al.Emerging swine flu is a kind of variant of classical H1N1 influenza virus infection and hence it is doubtless that swine flu can affect the sperm quality. At least, the acute febrile episode can affect the sperm. However, there exist no official reports on this aspect as well as the correlation between swine flu and infertility. Nevertheless, the presentation and effect of swine flu in infertile case has never been well explored.


Atopic dermatitis (AD) is a chronic pruritic skin disease. It results from a complex interplay between strong genetic and environmental factors. The aim of this work was to study some biochemical markers of the dermatosis. This included detection of R576 interleukin-4 receptor alpha allele gene. Twenty five patients with AD and 25 controls participated in this study. Atopic dermatitis (AD) is recognized as a strongly heritable chronic, pruritic inflammatory skin condition that is most common in early childhood and predominantly affects the skin flexures. Current evidence indicates that AD is strongly genetic, with enhanced levels of phenotype concordance reported in monozygotic relative to dizygotic twins. The indiAim of this study was to identify some immunological and chemical markers in AD and their relation to disease severity. Aim was also to detect genotype R576 IL-4 receptor α allele and to clarify its segregation with AD as well as its usefulness as clinical marker of the disease.et al, by using the Nottingham eczema severity score.[Twenty five patients with AD and 25 age and sex matched controls participated in this study. All the participants had received no antihistamines or systemic or topical corticosteroids during the period of three weeks before clinical evaluation (a wash-out period), and were subjected to skin-prick test. AD diagnosis was based on the criteria of Hanifin and Rajka. The sevety score.Twenty five healthy, nonatopic, age and sex matched, and unrelated volunteers comprised the control group. They were enrolled in the study if their skin testing were negative and after excluding history of allergic conditions.et al.[All subjects included in this study were subjected to the following: a complete clinical history was obtained followed by clinical examination. Stool and urine analysis was done to exclude parasitic infestations for its affect on eosinophil count and activity. Determinet al. Serum ILet al. Determinet al. Also, coet al. Serum toet al.Determination of R576 IL-4 α allele was by PCR-based restriction fragment length polymorphism.DNA was isolated using the PUREGENE DNA isolation kit purchased from Gentra. DNA was extracted according to the method of Bubbon.t-test, analysis 2 of variance (F-test), correlation coefficient, Chi-square (X2) test, exact Fisher exact, and Odds ratio and relative risk.The statistical method used for analysis of the data was according to Kirkwood. The statThe results of this study showed that the most common allergens causing positive skin test among atopic patients were mixed pollens (46.6%), hay dust (33.3%), smoke (21.3%), house dust mite (18.6%) and mixed fungus (16%), cotton and wool (9.3%), mixed feather (6.6%), and animal dander (5.3%).P < 0.001). There was also a significant association between homozygosity for the R/R576 allele and atopy (P = 0.02). The relative risk of R576 allele in atopy was 7.3. For homozygous R/R576, there was a statistical significance for the severe versus mild disease (P = 0.03) [P < 0.001). Also, there was no statistically significant difference between the serum IL-4 values and allelic variants in all atopic patients. There was a significant positive correlation between serum ECP and peripheral blood eosinophil cell count, and serum total IgE. There was no statistically significant correlation between serum IL-4 and serum ECP, peripheral blood eosinophils cell count, or total serum IgE (see tables).There was a statistically significant association between R576 allele and atopy as compared with control group ( = 0.03) . Levels  = 0.03) . There wThe present study supported the association of R576 allele with atopy severity  which haet al,[et al,[et al,[et al,[et al.[et al,[This result agreed with Deichmann et al, who had l,[et al, who had l,[et al, Beghe etl,[et al, and Hytol,[et al. It seemsl.[et al, had repoet al,[et al,[et al,[Rogala et al, hypothesl,[et al, have foul,[et al, have fouet al,[et al, could find no evidence of linkage or association of atopic asthma with R576 allele in Italian subjects. Whereas Haagerup et al,[The result regarding the association of R576 allele with atopy was in contradiction with Mitsuyasu et al, who had up et al, had founet al,[et al,[et al,[The result regarding the association of R576 allele with atopy markers agreed with Cui et al, who suggl,[et al, found sil,[et al, stated tl,[et al,32et al, Kandil et al, Joseph-Bowen et al, and Higashi et al.[In AD, there was a highly significant increase in serum ECP as compared to control group and there was a strong correlation between its level and disease severity. Similar results were obtained by Di Lorenzo hi et al.–36 Eosinhi et al.38 contaihi et al.40 Their In AD group, there was also a highly significant increase in serum total IgE as compared with the control group and there was a highly significant positive correlation between increased serum total IgE levels and Nottingham eczema severity scoring system. These results indicate that serum total IgE may be used as an indicator of AD and its severity, especially in the peak season of allergy. Significant higher levels of serum IgE have been found in other studies.42 Laske et al,[A majority of subjects identified as carrying a single copy of the mutant allele were found to have atopy, suggesting an intermediate dominant effect, with (increasing) homozygotes suffering more severely (gene dosage effect). However, the finding that some carriers of the R576 allele, including one who was homozygous, were not atopic, indicates that the penetrance of this allele may be modified by other factors. These may include distinct genetic loci that impart susceptibility to or protection from atopy, and environmental factors such as the level and duration of exposure to allergens. This reset al, a Frenchet al,[et al,[et al,[et al,[et al,[et al,[The suggested molecular mechanism underlying the observed enhanced signaling with Q576R mutation and the association with R576 allele with atopy is that the substitution of arginine for glutamine at position 576 alters the binding profile of the adjacent phosphorylated tyrosine residue (Y575) and decreases the binding of phosphotyrosine phosphatases (SHP-1). SHP-1 dephosphorylates regulatory phosphotyrosine residues and has been implicated in the termination of IL-4 receptor signaling leading to exaggerated IL-4 responses. Hershey et al, and Hansl,[et al, stated tl,[et al, who repol,[et al, noted thl,[et al, who suggl,[et al, reportedIt could be postulated that patients with atopy having R576 allele may express a more highly active variant of the IL-4R; this mutation may predispose persons to allergic diseases by altering the signaling function of the receptor. So, R576 allele acts as an allergic susceptibility and disease-modifying gene and may serve as a clinically useful marker of asthma severity as one or two copies of R576 allele were associated with more severe disease. R576 allele correlates with markers of atopy, namely: IgE, ECP and eosinophil count.


Several autoantibodies directed against cardiac cellular proteins including G-protein-linked receptors, contractile proteins and mitochondrial proteins, have been identified in patients with dilated cardiomyopathy (DCM). Among these autoantibodies, anti-β1-adrenoreceptor (AR) antibodies have long been discussed in terms of their pathogenetic role in DCM. Anti-β1-AR antibody-positive patients with DCM showed significant deterioration of NYHA functional class as well as reduced cardiac function compared to those in autoantibody-negative patients. Various studies with a limited number of patients indicate that the use of immunoadsorption to eliminate immunoglobulin G (IgG) significantly improves cardiac performance and clinical status in heart failure patients. Since removal of autoantibodies of the IgG3 subclass induces hemodynamic improvement and an increase in the left ventricular ejection fraction, antibodies belonging to IgG3 such as anti-β1-AR antibodies might play an important role in reducing cardiac function in patients with DCM. According to a recent report, however, the effect of hemodynamic improvement by immunoadsorption threapy was similar among patients who were positive and negative for anti-β1-AR antibodies, indicating that the beneficial effects of immunoadsorption might be not directly associated with the selective elimination of the β1-AR autoantibodies. Immunoadsorption therapy is a new therapeutic option for patients with DCM and heart failure, but further investigations are required to elucidate the specific antigens of cardiac autoantibodies responsible for the hemodynamic effects. Dilated cardiomyopathy (DCM) is a progressive myocardial disease characterized by contractile dysfunction and ventricular dilatation. DCM is not a rare cause of congestive heart failure and the leading reason for heart transplantation world wide . AlthougA variety of experimental studies suggest that alterations of the immune system might be involved in the pathogenesis of DCM . A numbeet al. [in vivo.Previously, Wallukat and his colleagues observed the immunoglobulin G (IgG) fraction in sera from DCM patients could induce a positive chronotropic effect on neonatal rat cardiac myocytes . That efet al.  also rep1) [An extremely high incidence of anti-β1-AR autoantibodies is also reported in end-stage DCM patients who require mechanical cardiac support . In sele1) . Further2). This IA for patients with DCM was first reported in an uncontrolled pilot study by Wallukat et al. [et al. [et al. [vs. conventional therapy. The treatment group underwent monthly IA followed by immunoglobulin substitution for 3 months. IA therapy led to a significant decrease in β1-AR autoantibody levels. The increase in LVEF and improvement of NYHA class were significantly greater in the treatment group compared with those in the control group. Muller et al. [et al. [Removal of β1-AR autoantibodies with immunoadsorption (IA) is achieved by passing a patient’s plasma over columns that remove immunoglobulins . It possesses nonselective physical features, but causes marked reduction of plasma levels of IgG3. In our protocol, plasma IgG and IgG3 levels dropped an average of 37% and 58% per single IA procedure, respectively.Previous studies used a variety of IA methods including specific anti-β1-AR antibody binding peptide columns  , nonspecet al.  reportedet al. . Those set al. [Usually IA was followed by intravenous immunoglobulin (IVIG) to prevent infectious complications that might arise from inappropriate lowering circulating IgG levels . Unlike et al.  did not et al. , and haset al. . They foet al. [et al. [Although IA is a new therapeutic option for patients with DCM, the mechanism of left ventricular functional benefit from IA is not known. IgG adsorption removes not only anti-β1-AR-autoantibodies but also all other potentially pathogenic autoantibodies affecting the heart in this class of immunoglobulins. Mobini et al.  has repoet al. . Schimke [et al.  reportedAccording to previous reports, the following questions remain to be resolved : First, Measurements of anti-β1-AR autoantibodies may be helpful for the monitoring of clinical status in patients with DCM. IA therapy to eliminate autoantibodies is a new and promising therapeutic option for those patients. However, further studies are necessary to elucidate the specific antigens of cardiac autoantibodies as well as cellular mechanisms responsible for the observed functional effects.


Sesamum indicum (EES), vitamin C (VC), and EES + VC in promoting fertility and finding a possible link between their profertility effects and their antioxidant activities.This study investigates the efficacy of ethanolic extract of G (EES only), VCG (vitamin C only), and EES + VCG (EES in conjunction with vitamin C). Control was given 5 ml/kg BW/day of normal saline orally; EESG was administered 0.3 g/kg BW/day of EES; VCG was administered 15 mg/kg BW/ day of VC; while EES + VCG was administered both 0.3 g/kg BW/day of EES and 15 mg/kg BW/day of VC. All treatments were for 10 weeks.Forty adult male Wistar rats [Body weight (BW) 186.56 ± 0.465 g] were randomly analyzed into four groups of ten rats each: Control, EESIndependent-sample T test was used to analyze the obtained results.The results obtained showed that EES, VC, and more importantly EES + VC are capable of significantly increasing BW gain, seminal parameters, testosterone level, and body antioxidant activities.These findings lead to the conclusion that EES + VC as well as ESS and VC promote fertility due to both their testosterone-increasing effects and their antioxidant effects. Because infertility are highly diversified in etiology, their treatments also require diversified approach. Some orthodox medications and traditional medications have proved really useful in the treatment of infertility. However,Sesamum indicum (EES) and citrus fruits [sources of vitamin C (VC)] to promote fertility. If we could establish that EES in conjunction with VC significantly promotes fertility, then there is a possibility that some cases of infertility could be treated cheaply with EES and VC. Many studies have also shown that antioxidants can enhance fertility either directly or indirectly and that most plants rich in antioxidants have the tendency to increase sperm counts, motility, and enhance sperm morphology. were randomly analyzed into four groups of 10 rats each: Control, EESTwenty-four hours after the last treatment, each animal was weighed and then sacrificed by cervical dislocation. Up to 4.0 ml blood samples were collected via cardiac puncture. Blood sample obtained from each rat was divided into two portions: 2.0 ml in a plain bottle and the other 2.0 ml in an ethylenediaminetetraacetic acid bottle. Plasma and serum were obtained by centrifugation at 3000 rpm for 20 minutes. Testis and caudal epididymis were excised from each rat.The left testis of each rat was homogenized  for tissue superoxide dismutase (SOD) and catalase (CAT) activities, and malondialdehyde (MDA) concentration. Sperm count, motility, morphology, and life-death ratio of the rats' spermatozoa were carried out from the epididymis. Serum testosterone level was determined. Plasma and tissue SOD and CAT activities, and MDA concentrations were determined using the methods described by Fridovich, Sinha,88 and VarP-value <0.05.The data obtained are presented as mean ± SD. The control and test groups were compared using Independent-sample T test. Significance level was taken at G group as well as EES + VCG was, however, significantly  higher than that of the control, while weight increase in VCG showed no significant difference from that of the control [Comparing their final and initial weights showed that there was significant body weight gain in all the groups over the period of the experiment. The weight gain in EES control .G showed no significant  difference from that of the control, while the testicular weight of EESG  and EES + VCG  was found to be significantly higher than that of the control [The testicular weight of VC control .G and EES + VCG treated animals was significantly  higher than that of the control, whereas SC for VCG alone showed no significant difference  from that of the control. Likewise, LDR of EESG and EES + VCG was found to be significantly  higher than that of the control, while VC showed no significant  difference from the control [SC for EES control .G and EES + VCG groups had SM that was significantly  higher than that of the control, whereas SM for VCG was not significantly  different from that of the control. SMP was, however, not significantly  different in all the test groups compared with the control [EES control .P-value <0.05) increase in STL in all the test groups compared to the control [There was significant  compared to the control [Plasma and testicular SOD activity were found to be significantly higher in all the treated groups  compared to the control, plasma CAT activity was only significantly  higher in EES + VCG [While testicular catalase (CAT) activity was found to be significantly higher in all the treated groups  compared to the control. In a similar way, testicular MDA concentration was found to be significantly lower in all the treated groups  compared to the control [Plasma Malondialdehyde (MDA) concentration was found to be significantly lower in all the treated groups  and in conjunction with VC (EES + VCG) significantly increases weight gain. The significant increase in weight gain in EESG can be linked to the high fat composition[et al.[et al.[Sesamum indicum significantly improved weight gain; and by Hanefy et al.[G reveals the possibility that EES in conjunction with VC have a synergistic effect on body weight, after all VC acting alone does not significantly affect body weight [Even though VC is very important for normal health condition by its antioxidant and detoxification actions, VC all b control . This isl [et al. On the cmposition and its on[et al. that metl.[et al. that Sesfy et al. that mety weight . A complet al.[et al.[et al.[The observed ability of VC to increase SC  is in liet al. that antl.[et al. that a bl.[et al.. Salawu l.[et al. earlier G was far higher than the LDR of all other groups [et al.[The life-death ratio (LDR) of the EES + VCr groups . This fus [et al. that antG [et al.[et al.[G was, however, lower than that of EES + VCG [The observed significant increase in SM and SMP in ESS + VCG  further G [et al. that VC l.[et al. The incrES + VCG . This juThe significant increase in both plasma and testicular SOD activity  and CAT et al.,[et al.,[et al.[VC acting alone, EES acting alone, and VC + EES acting together significantly increased blood testosterone level. This finding is parallel to the observations of Salawu et al., Ukwenya ,[et al., and Shit.,[et al. that ses.,[et al.–5 and th.,[et al..


The increasing availability of large-scale protein-protein interaction data has made it possible to understand the basic components and organization of cell machinery from the network level. The arising challenge is how to analyze such complex interacting data to reveal the principles of cellular organization, processes and functions. Many studies have shown that clustering protein interaction network is an effective approach for identifying protein complexes or functional modules, which has become a major research topic in systems biology. In this review, recent advances in clustering methods for protein interaction networks will be presented in detail. The predictions of protein functions and interactions based on modules will be covered. Finally, the performance of different clustering methods will be compared and the directions for future research will be discussed. Within cells, proteins seldom act as single isolated species to perform their functions. It has been observed that proteins involved in the same cellular processes often interact with each other . ProteinA protein interaction network is generally represented as an interaction graph with proteins as vertices (or nodes) and interactions as edges. Various topological properties of protein interaction networks have been studied, such as the network diameter, the distribution of vertex degree, the clustering coefficient and etc. These network analyses have shown that protein interaction networks have the features of a scale-free network -7 and “sClustering in protein interaction networks is to group the proteins into sets (clusters) which demonstrate greater similarity among proteins in the same cluster than in different clusters. In protein interaction networks, the clusters correspond to two types of modules: protein complexes and functional modules. Protein complexes are groups of proteins that interact with each other at the same time and place, forming a single multimolecular machine, such as the anaphase-promoting complex, RNA splicing and polyadenylation machinery, protein export and transport complexes, etc . FunctioRecently, many research works have been done on the problem of clustering protein interaction networks. These works rely on very different ideas and approaches. This paper tries to help readers keep up with recent and important developments in the field, and to give readers a comprehensive survey on the different approaches. This paper is organized as follows: At first, the graph-based clustering methods including the density-based and local search algorithms, the hierarchical clustering algorithms, and other optimization-based algorithms, are given in Section 2. Then the approaches of combination with other information are discussed and some ensembles are given in Section 3. In Section 4, the validation and comparison of the clustering methods are discussed. Then the application of the clustering methods for protein function prediction and protein-protein interaction prediction are given in Section 5. At last, challenges and directions for future research are discussed in Section 6.G, where vertices represent proteins and edges represent interactions. The relationship between two proteins can be the simple binary values: 1 or 0, where 1 denotes the two proteins interact and 0 denotes the two proteins do not interact. In such cases, the graph is unweighted. Sometimes, the edges of graph G are weighted with a value between 0 and 1. In such cases, the weight represents the probability that this interaction is a true positive.In general, a protein interaction network is represented as an undirected graph In recent years, various graph-based clustering algorithms have been developed for detecting protein complexes and functional modules in protein interaction networks. According to whether the algorithm can identify overlapping clusters, these algorithms can be classified into two types: Non-overlapping clusters detecting algorithms and overlapping clustering identifying algorithms. These algorithms can also be divided into the follows: density-based and local search algorithms, hierarchical clustering algorithms, and other optimization-based algorithms, according to different definition and ideas.Based on the assumption that the members in the same protein complex and functional module strongly bind each other, a cluster can be referred as a densely connected subgraph within a protein interaction network. Several algorithms for finding dense subgraphs have been proposed.d) of a subgraph with n vertices and m edges is generally defined as d=2m/(n(n-1))  is the maximal possible number of them. The idea behind the use of this definition in [et al[g as g built on the edge e and g.where ition in  is that chi et al develope al[g as  where  iet al[However, this definition is not feasible when the network has few triangles or higher order cycles. To avoid of the limitation, Li et al redefineuN is the set of neighbors of vertex u and vN is the set of neighbors of vertex v, respectively.where λ-module  denotes the weight of edge e, u,vI denotes the set of common vertices in uN and vN . Correspondingly, Li et al defined λ*-module of weighted protein interaction networks, as shown in Table λ *-module of weighted protein interaction networks can help improve the accuracy of clustering. Another contribution of their work is that FAG-EC and HC-Wpin can identify the functional modules in a hierarchy by changing the values of parameter λ and such hierarchical organization of modules approximately corresponds to the hierarchical structure of GO annotations. More attractive strength of FAG-EC and HC-Wpin is their efficiencies. The total time complexities of FAG-EC and HC-Wpin are both O(2mk). As is well known the scale-free of protein interaction networks, k is very small and can be considered as a constant. Thus, FAG-EC and HC-Wpin are very fast which can be used in large protein interaction networks as the protein-protein interactions accumulate.where et al[Recently, Wang et al combinedet al) and theet al.[et al.[et al. in [Besides the two typical metrics discussed above, a number of other metrics have also been suggested to be used in the hierarchical clustering algorithms. Hartuv and Shamir  used theet al. developel.[et al. suggestet al. in . They prThe definition of similarity metric or distance measure is a crucial step for hierarchical clustering. How to evaluate the metrics is another challenge in hierarchical clustering. Two evaluation schemes suggested by Lu et al, which are based on the depth of hierarchical tree and width of ordered adjacency matrix, may be useful. Moreover, Chen et al  gave a fThe obvious advantage of hierarchical clustering approach is that it can present the hierarchical organization of protein interaction networks. Its drawback is that it can not generate overlapping clusters except that special pre-processing or other strategies are used. In addition, the hierarchical clustering approaches are known to be sensitive to the noisy data in protein interaction networks .et al[In addition to the density-based and local search algorithms and hierarchical clustering algorithms, some other optimization-based algorithms are also frequently used. For example, King et al proposedet al.[Another optimization model for the discovery of clusters was proposed by Newman and Girvan , in whicet al. suggesteet al., and optet al., extremaet al., and speet al.-57.et al.[Recently, Hwang et al. presenteSTM consists of four steps :(1) Compute signals transduced between all vertex pairs;(2) Select cluster representatives for each vertex;(3) Formation of preliminary clusters;(4) Merge preliminary clusters.et al extended STM to CASCADE [In STM, the Erlang distribution is used to model the signal transduction behavior of the network. STM considers only the least resistance paths between protein pairs in a network and propagates the occurrence probability through a shortest path between a protein pair. More recently, Hwang  CASCADE , in whicet al[et al[Among others, the Markov Cluster Algorithm (MCL) ,61 has bet al transforet al, MCL waset al and RNSCet al. More reet al showed t al[et al have proet al.[et al[Furthermore, in the recent past, some novel optimal clustering approaches have been proposed for the discovery of protein complexes or functional modules. Mete et al., for exaal.[et al investigal.[et al in sociak-plex [k≤n/2, for a given k, where n was the number of vertices in the cluster, and the peripheries of a core was defined as the set of vertices that were not in the core and whose distances to any member in the core were equal to l .In recent years, much attention has been focused on the clustering algorithms for finding overlapping clusters. For the overlapping clusters, each protein may be involved in multiple complexes or functional modules. This is particularly true of protein interaction networks for most proteins having more than one biological function. Some of the above mentioned clustering algorithms, such as STM , can be et al.[k-clique percolation communities. A k-clique is a complete subgraph of size k. Two k-cliques are said to be adjacent, if they share exactly k-1 vertices. A cluster is defined as a union of all k-cliques that can be reached from each other through a series of adjacent k-cliques. Based on CPM, a powerful tool CFinder for finding overlapping clusters has been developed by Adamcsek et al.[k; 2) the proteins not included in any k-cliques are neglected. To overcome the disadvantages of CPM, people often adopt some pre-processing or post-processing when using it. Jonsson et al.[et al proposed two types of strategies: size control [k=3 to generate initial clusters and then iteratively used k+1 to separate the clusters of size larger than a given integer S until all the identified clusters of size were less than S.In 2005, Palla et al. investigek et al.. Though on et al. construc control  and line control  when usiet al[et al[et al[Zhang et al suggeste al[et al proposed al[et al proposedet al.[Another method based on clique for identifying overlapping clusters is COD (Complex Overlap Decomposition) proposed by Zotenko et al.. COD reqet al.. The veret al.[et al.[et al.[et al.[et al. combined the flow-based approach with two new metrics: semantic similarity and semantic interactivity, where Gene Ontology (GO) annotations were used to weight protein-protein interactions. Different methods adopted for the selection of essential proteins will result in different overlapping clusters. Thus, to select the informative vertices more exactly will help to identify the overlapping clusters more accurately.The essential proteins have always been counted as having a close connection to the overlapping clusters -82.Typicet al. proposedl.[et al. suggestel.[et al. developel.[et al.,82 was al.[et al.. Later il.[et al., Cho et et al[Moreover, some extended hierarchical clustering algorithms can also be used for the identification of overlapping clusters. Pinney et al, for inset al based onIn addition, the algorithms of detecting overlapping community structures in other complex networks, such as fuzzy clustering , EAGLE , and nodThe above discussed methods for identifying clusters are mostly based on graph theoretic properties solely and only require the protein-protein interaction data. Unfortunately, protein interaction networks, as we all know, can not avoid of the false positives and false negatives . To lesset al.[et al.[et al.[Jiang and Keating  describeet al. integratl.[et al. developel.[et al. presenteet al.[et al.[Jung et al. presenteet al., a tool l.[et al. extractel.[et al. and LCMAl.[et al., to estiet al.[et al.[et al.[et al.[et al.[et al.[et al.[Owing to the attribute that members in a cluster typically perform a specific biological function , severalet al. related l.[et al. proposedl.[et al. developel.[et al.. Segal el.[et al. introducl.[et al. presentel.[et al. also intl.[et al.. Recentll.[et al. proposedMore recently, Ulitsky and Shamir  transforet al.[et al.[Except for gene expression data, authors also usually combined protein interaction networks with GO annotations. Typically, the flow-based approach proposed by Cho et al., as alrel.[et al. suggestel.[et al. mapped kWith the rapidly expanding resource of microarray data and other biological information, such as structure profiles  and phylet al.[Ensemble clustering ,109 has k-way partitioning, and multilevel k-way partitioning, with two topology driven distance metrics were used to obtain six base clusterings, and then a consensus method based on Principal Component Analysis (PCA) was developed to reduce the dimensionality of the consensus problem. Asur et al.[In , initialur et al. also deset al.[et al.[Another ensemble framework for clustering protein interaction networks was proposed by Greene et al.. They fiet al. was adopet al.. Consensl.[et al. was a soAs being in nascent stage, ensemble clustering approach inevitably faces some challenges for the discovery of protein complexes and functional modules. A series of crucial factors, such as choosing the basic clustering methods, building a consensus, and adapting for soft clustering, must be taken into account carefully.Biological validation of the predicted clusters in protein interaction networks is very essential. As previous discussed, disparate results can be obtained from the same protein interaction network with different algorithms or even with the same algorithm where different parameters are chose. Therefore, different solutions must be carefully compared in order to select the approach and parameters which provide the best outcome. Validation is a process of evaluating the performance of the clustering or prediction results derived from different approaches. This section will introduce several basic validation approaches for clustering in protein interaction networks.Previous studies have showed that proteins in the same cluster often have high functional homogeneity . The funC contains k proteins in the functional group F, and the entire protein interaction network contains |V| proteins. P-value with a hypergeometrical distribution shows the probability that a given set of proteins is enriched by a given functional group merely by chance. Smaller P-value indicates that the predicted cluster is not accumulated at random and is more significant biologically than one with a larger P-value. The function annotation can be obtained from MIPS [where the predicted cluster rom MIPS  or GO , has been suggested to quantify the overall clusters.Sn and In denotes the number of significant and insignificant clusters, respectively and min(pi) denotes the smallest P-value of the significant clusters i (i=1 to n). The cutoff is used to distinguish a significant cluster from insignificant clusters. We say a cluster is significant if its corresponding smallest P-value is lower than the cutoff value.where Another method for assessing the functional homogeneity of proteins within a predicted cluster is redundancy , as shown represents the number of classes in the classification scheme, and sprepresents the relative frequency of the class in the predicted cluster. All values of R lie between 0 and 1. With this scoring system, clusters containing many proteins with highly consistent classifications will receive high scores (R closer to 1), whereas those with disparate or conflicting classifications will receive low scores (R closer to 0).where Pc) and the known complexes (Kc) is often done. The gold-standard data used as known complexes are available form those catalogued in the MIPS database [OS between a predicted cluster Pc and a known complex Kc is generally calculated by formula (9) [To evaluate the performance of algorithms for clustering in protein interaction networks, a comparison of the predicted clusters (database . The ovemula (9) ,21,22: is larger than a specific threshold δ. Generally, 0.2 is used in the literature [where |terature .Sn=TP/(TP+FN), where TP (true positive) is the number of the predicted clusters matched by the known complexes with OS≥δ, and FN  is the number of the known complexes that are not matched by the predicted clusters [Sp=TP/(TP+FP), where FP  is equal to the total number of the predicted clusters minus TP. Generally, another integrated method, called f-measure, as shown in formula (10) [Obviously, known complexes and predicted clusters are expected to be matched as many as possible. Sensitivity and specificity ,22 are tclusters ,22. SpecolP of a random overlap between them. The olP is defined as:Also, we can determine a best matched known complex for a predicted cluster by minimizing the probability i is the number of the common proteins between the predicted cluster Pc and the known complex Kc. The smaller the olP is, the more consistent they are.where T, as that has been done by Brohée and Helden [n known complexes and m predicted clusters, the contingency table is a n*m matrix where row i corresponds to the thi known complex, and column j to the thj cluster. The value of a cell ijT indicates the number of common proteins that appear both in complex i and cluster j. In addition, some other measurements, such as positive predictive value (PPV), accuracy, and separation, can also be used to evaluate the match between a set of known complexes and a clustering result. More details about these measurements, the reader are referred to [One can also match the clustering result with the known protein complexes by building a contingency table d Helden . Given nerred to .et al., generally tend to share similar temporal expression profiles, subcellular localizations, and gene phenotypes, which support the functional relevance of modular organization. Moreover, the robustness of a clustering algorithm can be validated by different levels of graph alterations, such as proportions of edges added or deleted at random can be used to test the algorithm’s robustness against the false positives and false negatives.Besides the above measurements, a comparison of the clustering results performed on protein interaction networks and on random networks is usually used. The random network requires having the same size and the same degree distribution as the original protein interaction network. Generally, one can get a corresponding random network by shuffling the edges between vertices in the original network ,22. SomeUp to now, there have been few special works for quantitative evaluation of the clustering algorithms except for some comparison works that have been done in each proposed algorithm for demonstrating its validity. Only in 2006, a systematic quantitative evaluation of four clustering algorithms: MCL ,61, MCODet al.[Tuji et al. comparedet al., a densiet al., a hieraet al.[Typical applications of clustering protein interaction networks are protein function prediction and protein-protein interaction prediction. For a cluster, as pointed by Hartwell et al., its memet al.[As there exits a large number of function-unknown proteins, even for the most well-studied yeast, about one-fourth of the proteins remain uncharacterized , and theet al. have givet al.[et al.[It is well known that the protein-protein interaction data available now are incomplete, though a number of high-throughput biotechnologies have been applied to biological systems. Recently, a series of computational methods have been developed for predicting protein-protein interaction data ,121. Espet al. predictel.[et al. suggesteClustering protein interaction networks can be used not only for predicting false negatives, but also for purifying false positives, as shown in Fig.In the post-genomic era, an important work is to analyze biological systems from network level, in order to understand the topological organization of protein interaction networks, identify protein complexes and functional modules, discover functions of uncharacterized proteins, and obtain more exact networks. To achieve this aim, a series of clustering approaches have been proposed. For different types of clustering algorithms, each has its own advantages and disadvantages. Every algorithm has certain problems while it exhibits good performances in other cases. The main challenges for clustering protein interaction networks are identified as follows:(1) Up to now, all methods for predicting protein-protein interactions are known to yield a nonnegligible amount of noise  and to miss a fraction of existing interactions  . Therefo(2) Clusters of a protein interaction network may overlap with each other. Most proteins have more than one molecular function and participate in more than one biological process. For example, some proteins form transient associations and are part of several complexes at different stages. Most cellular processes are carried out by multi-protein complexes. Therefore, the traditional clustering approaches of putting each protein into one single cluster do not suit this problem well. Moreover, how heavily two clusters should overlap with each other is not certain.(3) Recent advances in the development of high-throughput techniques have led to an unprecedented amount of protein-protein interaction data becoming available in a variety of simple organisms. It is computationally difficult for most of current clustering algorithms to accurately identify protein complexes or functional modules from large-scale protein interaction networks, especially to discover meso-scale clusters.(4) There are little priori knowledge for clustering protein interaction networks, such as cluster number and cluster size. How many clusters should we produce? How large are clusters suitable? How to validate different clustering results with various sizes? These are all challenges for designing effective clustering algorithms.(5) Current clustering approaches mainly focus on detecting clusters in static protein interaction networks for most existing biological data are static. However, both the protein-protein interactions and protein complexes are dynamically organized when implementing special functions. Dynamic modules generally correspond to the sequential ordering of molecular events in cellular systems. How to explore dynamic modules from static protein interaction networks is a very difficult task.et al.[While some clustering approaches have been applied successfully in the discovery of protein complexes or functional modules, methods for clustering and analyzing protein interaction networks are less mature. Particularly, the methods for identifying dynamic modules are in a nascent stage. Methods which use time-series gene expression profiling data to manifest the temporal complexity of protein interaction networks may be useful to the exploration of dynamic modules. For example, Li et al. have sucet al. may alsoFurthermore, techniques and methods for developing both robust and fast clustering algorithms are directions for further researches. In the future, “overlap” will continue to be a hot topic for clustering protein interaction networks, which include how many molecular functions a protein can perform, how many biological processes a protein can participate in, and how many cellular components a protein can be associated with or located in. Moreover, we should investigate the question that if there some relationship between the two properties: overlapping and hierarchical organization of clusters, which were usually taken into account separately before. Some works have been done in complex networks, such as word association networks and scientific collaboration networks , to deteThe authors declare that they have no competing interests.JW and ML drafted the manuscript together. YD and YP participated in revising the draft. All authors have read and approved the manuscript.


Stroke in young poses a major health problem. Thrombophilic factors have been implicated in 4-8% of the young strokes worldwide. Protein S deficiency is a rare cause of recurrent ischemic stroke in young population. Only a few sporadic cases have been described in the literature. We are reporting a case of protein S deficiency-related recurrent ischemic stroke in a 16-year-old girl. Early diagnosis and targeted approach can help such patients to prevent recurrent thrombotic episodes. Protein S is a naturally occurring vitamin K-dependent protein, which in conjunction with active protein C, inhibits the clotting cascade. Protein S deficiency is known to be of clinical significance in patients with deep venous thrombosis or pulmonary emboli. The overall estimated incidence of deep vein thrombosisis is one episode for every 1,000 persons. Protein S deficiency has been also found to be associated with cerebrovascular occlusion, although the exact role is controversial.A 16-year-old girl presented with acute onset left sided hemiparesis without loss of consciousness. General physical examination was unremarkable. Neurological examination revealed findings consistent with left-sided hemiparesis. A similar episode occurred three years back. No precipitating factors such as chronic drug intake were present. Family history was negative for vascular events or other predisposing factors for stroke.CT head  revealedWorkup for thrombophilias revealed reduced protein S function  alongwith protein C; whereas, antithrombin III, anticardiolipin antibodies, and lupus anticoagulant were within normal limits. A diagnosis of protein S deficiency was kept and the patient was managed with intravenous heparin followed by oral anticoagulants. Neurological functions improved and patient was discharged on oral anticoagulants. Repeat thrombophilic profile after three months revealed protein S functional activity 42% of the normal with patient showing remarkable recovery.et al.[et al.[et al.[Stroke in young population has a high incidence of approximately 24–35%, according to some studies in India. Abraham et al. from Velet al.[et al.[et al.[et al.[et al.[The importance of thrombophilic disorders in arterial stroke has been debatable. Ischemic stroke has been reported as a rare manifestation of protein S deficiency. Girolami et al. and Sie l.[et al. were amol.[et al. studied l.[et al.–9 Douay l.[et al. reportedIn this 16-year-old patient without any risk factors, the acquired factor S deficiency possibly played a role in the recurrent ischemic stroke. Factor S deficiency should be considered in venous stroke, recurrent pulmonary embolism, unusual site of venous occlusion, family history of vascular events, and stroke in young population. Aetiology of such vascular events in young must be thoroughly investigated so as to guide prevention and treatment of this devastating disease. Measurement of total and free protein S levels should be a part of the evaluation for any young adult who has had a stroke.


This review is focused on molecular momentum transport at fluid-solid interfaces mainly related to microfluidics and nanofluidics in micro-/nano-electro-mechanical systems (MEMS/NEMS). This broad subject covers molecular dynamics behaviors, boundary conditions, molecular momentum accommodations, theoretical and phenomenological models in terms of gas-solid and liquid-solid interfaces affected by various physical factors, such as fluid and solid species, surface roughness, surface patterns, wettability, temperature, pressure, fluid viscosity and polarity. This review offers an overview of the major achievements, including experiments, theories and molecular dynamics simulations, in the field with particular emphasis on the effects on microfluidics and nanofluidics in nanoscience and nanotechnology. In Section 1 we present a brief introduction on the backgrounds, history and concepts. Sections 2 and 3 are focused on molecular momentum transport at gas-solid and liquid-solid interfaces, respectively. Summary and conclusions are finally presented in Section 4. Feynman at the 1959 annual meeting of the American Physical Society –9. Motor−1, while that for a MEMS device with a size of 1 μm is 106 m−1 and for a NEMS device having a length of 1 nm is 109 m−1. The large surface to volume ratio for MEMS and NEMS devices enables factors related to surface effects to dominate the fluid flow physics at micrometer to nanometer scales , Lauga et al. [r:T0 is the reference temperature, β is a dimensionless coefficient of order one, v is the fluid kinetic viscosity, Tk is the fluid thermal diffusivity, and pc is the specific heat. The shear-dependent slips observed in Ref. [High shear rates also induce viscous heating as a result of the dissipation of mechanical energy. The viscous heating then inevitably results in temperature increase and viscosity decrease of the liquids. Considering a traditional exponential law for the liquid viscosity a et al.  proposed in Ref.  by the C3.3.4.et al. reported that slip was not observed in vacuum conditions but only when the liquid sample was in contact with air in their sedimentation experiments. In Ref. [et al. reported that tetradecane saturated with CO2 resulted in no-slip but with argon resulted in significant slip. In Ref. [et al. calculated the slip lengths for liquid flows between two infinite parallel plates by modeling the presence of either a depleted water layer or nanobubbles as an effective air films at the walls and found the results were consistent with some experimental measurements. Using patterned surfaces to trap gases, Refs. [Many measured apparent slips were ascribed to the presence of small amount of gas trapped or pinned on rough, patterned and/or hydrophobic surfaces ,352–354. In Ref. , Granick In Ref. , Trethews, Refs. ,219,256 et al. [et al. [et al. performed shock wave induced cavitation experiments and atomic force microscopy measurements of flat polyamide and hydrophobized silicon surfaces immersed in water and showed that surface nanobubbles were not just stable under ambient conditions but also under enormous reduction of the liquid pressure down to −6 MPa. This implied that surface nanobubbles were unexpectedly stable under large tensile stresses.In 1983 Ruckenstein et al.  proposedet al. ). Detailet al. . Some reet al. –376 conc [et al.  found th [et al. ,377–382. [et al. , Borkentμ1 flowing over a layer of height h with viscosityμ2, the apparent slip length is [The apparent slip length will be very large when considering liquid flows over gas films. Considering a liquid of viscosity ength is :(63)Ls μ1/μ2 ≈ 50. As pointed out in Ref. [μ is the viscosity of the liquid, ρ is the density of the gas, and thu is the thermal velocity of the gas. The apparent slip length is independent of the gas film thickness.For gas-water interfaces  in Ref. , there a in Ref. :(64)Ls et al. [et al. [et al. [Exceptions should also be noted. Steinberger et al.  stated t [et al.  proposed [et al.  investig3.3.5.3.3.5.1.et al. [Cho et al.  studied et al.  slip waset al.  the morp3.3.5.2.et al. [et al. [Apparent slip lengths are thought to arise in a thin layer of liquids with lower viscosity near the wall of a smooth solid surface or in regions of higher shear next to the peaks and ridges of a rough solid . Howeveret al.  reported [et al.  showed l [et al. .3.3.5.3.et al. reported that the slip lengths, either for normal slip or stick slip, usually decreased with increasing temperature using molecular dynamics simulations. From Lauga et al.’s model for the slip length  slip at macroscopic level measured by experiments. The microscopic slip length is about nanometers. The macroscopic slip length, however, spans nanometers to micrometers. Therefore, a challenge for deepening related researches is that they are incompatible in magnitude as well as in physical mechanisms. Frankly speaking, the physical mechanisms for liquid slip over solid surfaces still remain obscure at the moment.The boundary conditions of liquid flows over solid surfaces depends on various physical factors, such as surface wettability, roughness, patterns, liquid shear rate, polarity, temperature and pressure. Molecular behaviors affected by many factors are unclear. It is necessary, but still a challenge to decouple their influences. Results obtained by different experimental techniques are often very different due to the large uncertainty in the measurements at nanoscale. Therefore, more novel experimental techniques to detect molecular behaviors near liquid-solid surfaces more accurately should be developed. More measurements and molecular dynamics simulations are needed.The molecular dynamics simulation method is a powerful tool to detect molecular behaviors near solid surfaces, keeping in mind the long distance from the experimental measurements. The disadvantages of this method includes that it often deals with very ideal liquid-solid surfaces and the computational expense of large scale systems is heavy. It is highly desired for molecular dynamics simulations to consider real liquid and solid situations. Large scale computation using high quality computers will be useful for molecular dynamics simulations to simulate micrometer scale systems. Other particle-based techniques, such as lattice-Boltzmann and atomistic-continuum hybrid methods, are also necessary alternatives.We are convinced that wettability and surface roughness (patterns) may be the most important factors affecting the molecular momentum transport between liquid and solid at interfaces. From this point of view, we will be able to prepare surfaces and channels in engineering with known and controllable boundary conditions, and consequently control the friction of micro- and nanoflows. Perhaps using surface patterns to trap gases and using surface coatings to artificially change the wettability are most feasible. Therefore, there leaves more open questions on formation mechanisms, physical properties and lifetime of the surface patterns trapped nanobubbles to researchers. Carbon nanotubes with rare fluid transport efficiency, as well as good electrical, optical, thermal and mechanical properties, will be a promising platform for microfluidics and nanofluidics engineering in MEMS/NEMS in the future.


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