Topical preparations for the treatment of mild-to-moderate acne vulgaris: systematic review and network meta-analysis.

BACKGROUND: Acne is very common and can have a substantial impact on wellbeing. Guidelines suggest first-line management with topical treatments, but there is little evidence regarding which treatments are most effective. OBJECTIVES: To identify the most effective and best tolerated topical treatments for acne using network meta-analysis. METHODS: CENTRAL, MEDLINE, Embase and World Health Organization Trials Registry were searched from inception to June 2020 for randomized trials that included participants with mild/moderate acne. Primary outcomes were self-reported improvement in acne, and trial withdrawal. Secondary outcomes included change in lesion counts, Investigator's Global Assessment, change in quality of life and total number of adverse events. Network meta-analysis was undertaken using a frequentist approach. Risk of bias was assessed using the Cochrane Risk of Bias Tool and confidence in evidence was assessed using CINeMA. RESULTS: A total of 81 papers were included, reporting 40 trials with a total of 18 089 participants. Patient Global Assessment of Improvement was reported in 11 trials. Based on the pooled network estimates, compared with vehicle, benzoyl peroxide (BPO) was effective (35% vs. 26%) for improving self-reported acne. The combinations of BPO with adapalene (54% vs. 35%) or with clindamycin (49% vs. 35%) were ranked more effective than BPO alone. The withdrawal of participants from the trial was reported in 35 trials. The number of patients withdrawing owing to adverse events was low for all treatments. Rates of withdrawal were slightly higher for BPO with adapalene (2·5%) or clindamycin (2·7%) than BPO (1·6%) or adapalene alone (1·0%). Overall confidence in the evidence was low. CONCLUSIONS: Adapalene in combination with BPO may be the most effective treatment for acne but with a slightly higher incidence of withdrawal than monotherapy. Inconsistent reporting of trial results precluded firmer conclusions.

Impacts of acute hepatopancreatic necrosis disease on commercial shrimp aquaculture.

Acute hepatopancreatic necrosis disease (AHPND) has caused severe losses in farmed populations of marine shrimp Penaeus vannamei and P. monodon. The causative agents are unique strains of the bacteria Vibrio parahaemolyticus and related Vibrio species. The disease emerged in the People's Republic of China (China) and Vietnam in 2010 and spread throughout South-East Asia; it was later reported in countries in both North and South America. The disease has had significant economic impacts on the shrimp aquaculture industry. From 2010 to 2016, combined losses from China, Malaysia, Mexico, Thailand and Vietnam due primarily to outbreaks of AHPND, including losses at the farm gate and those resulting from a drop in feed sales and exports, were estimated at over US$ 44 billion. Other economic losses include those associated with processing facilities, decreased community revenues resulting from increased unemployment, financial investments, and the costs of implementing diagnostic and control measures. The reduced employment opportunities and increases in debt burden and investment risk have had sociological impacts. The responses to the disease have led to a gradual recovery of the shrimp industry in affected countries. These response efforts have included the implementation of changes in farming systems and management, including, among others, enhanced biosecurity and the use of AHPND-free and AHPND-resistant shrimp. This situation of losses and recovery illustrates the importance of having a multi-level response plan in place to prevent, or to reduce the risk of, outbreaks of disease.

La maladie de nécrose hépatopancréatique aiguë (AHPND, selon ses sigles en anglais) a occasionné des pertes importantes dans les élevages des espèces de crevettes marines Penaeus vannamei et P. monodon. La maladie est causée par des souches particulières de la bactérie Vibrio parahaemolyticus et d'autres espèces apparentées de Vibrio. Apparue en 2010 en République populaire de Chine et au Vietnam, la maladie s'est d'abord propagée dans toute l'Asie du SudEst avant d'être notifiée dans plusieurs pays d'Amérique du Nord et du Sud. Ses conséquences économiques sont très lourdes pour le secteur de la pénéiculture. On estime à plus de 44 milliards de dollars US les pertes cumulées enregistrées entre 2010 et 2016 par la Chine, la Malaisie, le Mexique, la Thaïlande et le Vietnam suite aux foyers d'AHPND (il s'agit aussi bien des pertes directes subies par les exploitations que de celles résultant de l'effondrement des ventes et des exportations d'aliments pour les élevages). D'autres pertes économiques sont associées aux établissements de transformation, aux pertes de revenus au sein des communautés locales par suite de l'augmentation du chômage, au déclin des investissements et aux coûts du diagnostic et des mesures de contrôle de la maladie. La réduction des perspectives d'emploi et l'augmentation du poids de la dette et des risques liés aux investissements ont affecté la société dans son ensemble. La mise en place de mesures appropriées a permis un redressement progressif du secteur de l'élevage de crevettes dans les pays atteints. Parmi ces mesures figurent les changements introduits dans les systèmes d'élevage et de gestion, en particulier l'amélioration de la biosécurité et l'utilisation de crevettes résistantes à la maladie ou indemnes. La situation décrite concernant ces pertes et ce redressement illustre l'importance de disposer d'un plan d'action à plusieurs niveaux afin de prévenir ou de réduire le risque de foyers.

La enfermedad de la necrosis hepatopancreática aguda (AHPND por sus siglas en inglés) ha infligido enormes pérdidas a las poblaciones de cultivo de camarones marinos de las especies Penaeus vannamei y P. monodon. Sus agentes etiológicos son determinadas cepas de las bacterias Vibrio parahaemolyticus y otras especies emparentadas del género Vibrio. La enfermedad apareció en 2010 en la República Popular de China y Vietnam y desde allí se propagó por todo el Sudeste asiático. Ulteriormente se notificó su presencia en Norteamérica y Sudamérica. La enfermedad ha tenido considerables consecuencias económicas para la industria camaronícola. El total de las pérdidas sufridas entre 2010 y 2016 por China, Malasia, México, Tailandia y Vietnam debidas principalmente a brotes de AHPND, sumando las sufridas en la explotación y las resultantes de la caída de las ventas de piensos y de las exportaciones, ascendieron según los cálculos a más de 44 000 millones de dólares estadounidenses. A estas pérdidas económicas se agregan otras, como las sufridas por las instalaciones de procesamiento, la caída de la renta comunitaria por el aumento del desempleo, la disminución de las inversiones financieras o los costos de aplicar medidas de diagnóstico y control. La reducción de las oportunidades de empleo y el aumento de la carga de la deuda y del riesgo de inversión han tenido también consecuencias sociológicas. Gracias a las medidas de lucha adoptadas, que trajeron consigo una serie de cambios en los sistemas acuícolas y en su gestión, entre ellos la mejora de la seguridad biológica y el uso de camarones no infectados y resistentes a la enfermedad, el sector camaronícola de los países afectados se ha ido recuperando gradualmente. Esta dinámica de pérdida y recuperación pone de manifiesto la importancia de tener instituido un plan de respuesta en múltiples eslabones para prevenir brotes de la enfermedad o reducir el riesgo de que se produzcan.

Upregulation of the ALDOA/DNA-PK/p53 pathway by dietary restriction suppresses tumor growth.

Dietary restriction (DR) delays the incidence and decreases the growth of various types of tumors; however, the mechanisms responsible for DR-mediated antitumor effects have not been unequivocally identified. Here, we report that DR suppresses xenograft tumor growth by upregulating a novel signaling pathway. DR led to upregulated aldolase A (ALDOA) expression in xenograft tumors. ALDOA physically interacted with the catalytic subunit of DNA-dependent protein kinase (DNA-PK) and promoted DNA-PK activation. Activated DNA-PK phosphorylated p53 and increased its activity. Although ALDOA can function as an oncogene in cultured cells, it can also activate the tumor suppressor p53. Thus, ALDOA overexpression in the presence of p53 suppressed xenograft tumor growth; however, when p53 was suppressed, ALDOA overexpression promoted xenograft tumor growth. Moreover, we demonstrated that p53 suppression inhibited the antitumor effects of DR. Our results indicate that upregulation of the ALDOA/DNA-PK/p53 pathway is a mechanism accounting for the antitumor effects of DR.

The interferon-gamma (IFN-γ) +874T allele reduces the risk of hepatitis B infection in an Asian population.

Increasing evidence suggests that polymorphism of the interferon-gamma (IFN-γ) gene in the first intron at position +874 may be associated with chronic hepatitis B virus (HBV) infection and/or HBV clearance. However, the results of relevant studies have been inconsistent. To derive a more precise estimation of the association, we performed a meta-analysis. In total, 10 independent studies including 1661 chronic HBV-infected patients and 1142 controls were included in this meta-analysis. In studies following Hardy-Weinberg equilibrium (HWE), a significantly decreased risk of chronic HBV infection was associated with the IFN-γ + 874TT genotype in the overall population (TT vs AA: odds ratio (OR) = 0.714, 95% confidence interval (CI) = 0.526-0.969, P = 0.031) when compared with a spontaneously recovered population. Subgroup analysis by ethnicity revealed a similar association in Asian individuals (TT vs AA: OR = 0.706, 95% CI = 0.518-0.962, P = 0.028). Moreover, when compared with a healthy control group, the 874T allele was associated with a significant lower risk of chronic HBV infection in the overall populations (TA vs AA: OR = 0.439, 95% CI = 0.193-0.997, P = 0.049; TT + TA vs AA: OR = 0.475, 95% CI = 0.271-0.832, P = 0.009) and in Asian individuals (TA vs AA: OR = 0.862, 95% CI = 0.744-0.999, P = 0.048). In conclusion, the IFN-γ + 874TT genotype and 874T allele reduce the risk of chronic HBV infection in Asian individuals.

Relationship between IL-10 gene -1082A/G and -592C/A polymorphisms and the risk of hepatitis C infection: a meta-analysis.

Increasing evidence suggests that interleukin-10 (IL-10) gene promoter polymorphisms may be associated with chronic hepatitis C virus (HCV) infection and HCV clearance. To more precisely estimate the association between these variants and the risk of HCV infection, we performed a meta-analysis of 26 studies describing the IL-10-1082A/G, -819C/T, -592C/A genotypes, including 4039 chronic HCV infection cases and 2902 controls. When compared with a healthy population, the -1082GG allele had a 43% increased risk of chronic HCV infection in combined populations (GG vs GA + AA: odds ratio (OR) = 1.433, 95% confidence interval (CI) = 1.052-1.952, P = 0.023). In subgroup analysis by ethnicity, a significant increased risk was associated with the -1082GG genotype in the Caucasian population (GG vs AA: OR = 1.390, 95% CI: 1.108-1.744, P = 0.004; GG vs GA + AA: OR = 1.621, 95% CI: 1.267-2.075, P = 0.000). However, no significant association was found in Asian, African or Chinese populations. Moreover, a higher distribution of -592A was found in the spontaneously recovered population (AA vs CC: OR = 0.585, 95% CI = 0.387-0.884, P = 0.011; AA + AC vs CC: OR = 0.738, 95% CI = 0.551-0.988, P = 0.041; AA vs AC + CC: OR = 0.788, 95% CI = 0.664-0.935, P = 0.006) than that in the chronic HCV infection population. In conclusion, the IL-10-1082GG allele may increase the risk of chronic HCV infection in Caucasian population, and people carrying the IL-10-592A allele are more likely to clear HCV spontaneously.

Historic emergence, impact and current status of shrimp pathogens in the Americas.

Shrimp farming in the Americas began to develop in the late 1970s into a significant industry. In its first decade of development, the technology used was simple and postlarvae (PLs) produced from wild adults and wild caught PLs were used for stocking farms. Prior to 1990, there were no World Animal Health Organization (OIE) listed diseases, but that changed rapidly commensurate with the phenomenal growth of the global shrimp farming industry. There was relatively little international trade of live or frozen commodity shrimp between Asia and the Americas in those early years, and with a few exceptions, most of the diseases known before 1980 were due to disease agents that were opportunistic or part of the shrimps' local environment. Tetrahedral baculovirosis, caused by Baculovirus penaei (BP), and necrotizing hepatopancreatitis (NHP) and its bacterial agent Hepatobacterium penaei, were among the "American" diseases that eventually became OIE listed and have not become established outside of the Americas. As the industry grew after 1980, a number of new diseases that soon became OIE listed, emerged in the Americas or were introduced from Asia. Spherical baculovirus, caused by MBV, although discovered in the Americas in imported live Penaeus monodon, was subsequently found to be common in wild and farmed Asian, Australian and African penaeids. Infectious hypodermal and hematopoietic necrosis virus (IHHNV) was introduced from the Philippines in the mid 1970s with live P. monodon and was eventually found throughout the Americas and subsequently in much of the shrimp farming industry in the eastern hemisphere. Taura syndrome emerged in Penaeus vannamei farms in 1991-1992 in Ecuador and was transferred to SE Asia with live shrimp by 1999 where it also caused severe losses. White Spot Disease (WSD) caused by White spot syndrome virus (WSSV) emerged in East Asia in ∼1992, and spread throughout most of the Asian shrimp farming industry by 1994. By 1995, WSSV reached the eastern USA via frozen commodity products and it reached the main shrimp farming countries of the Americas located on the Pacific side of the continents by the same mechanism in 1999. As is the case in Asia, WSD is the dominant disease problem of farmed shrimp in the Americas. The most recent disease to emerge in the Americas was infectious myonecrosis caused by IMN virus. As had happened before, within 3years of its discovery, the disease had been transferred to SE Asia with live P. vannamei, and because of its impact on the industry and potential for further spread in was listed by the OIE in 2005. Despite the huge negative impact of disease on the shrimp farming industry in the Americas, the industry has continued to grow and mature into a more sustainable industry. In marked contrast to 15-20years ago when PLs produced from wild adults and wild PLs were used to stock farms in the Americas, the industry now relies on domesticated lines of broodstock that have undergone selection for desirable characteristics including disease resistance.

A real-time PCR for the detection of hepatopancreatic parvovirus (HPV) of penaeid shrimp.

Hepatopancreatic parvovirus (HPV) causes a common shrimp disease that occurs in many shrimp farming regions, especially in the Indo Pacific, and infects most of the cultured penaeid species. There are seven geographic HPV isolates known, so a method to detect different HPV types is needed. We developed a sensitive and generic real-time PCR assay for the detection of HPV. A pair of primers and TaqMan probe based on an HPV sequence obtained from samples of Fenneropenaeus chinensis from Korea were selected, and they were used to amplify a 92 bp DNA fragment. This real-time PCR was found to be specific to HPV and did not react with other shrimp viruses. A plasmid (pHPV-2) containing the target HPV sequence was constructed and used for determination of the sensitivity of this assay. The assay could detect a single copy of plasmid DNA, and it was used successfully in finding HPV in shrimp samples from the China-Yellow Sea region, Taiwan, Korea, Thailand, Madagascar, New Caledonia and Tanzania.

Integrated centralized utility services to a chemical complex on Jurong Island, Singapore.

SUT pioneered centralized utility services for the chemical industry on Jurong Island, which are cost-effective due to economies of scale, reliable due to inter-connection of satellite operations, and customer tailored for special requirements. The utility services range from the supply of steam and water, wastewater treatment, incineration, terminalling, service corridor to fire fighting. Among the services, water management achieves the complete cycle from wastewater treatment to effluent recycling.

Detection and quantification of infectious hypodermal and hematopoietic necrosis virus in penaeid shrimp by real-time PCR.

A real-time PCR method using a fluorogenic 5' nuclease assay and a PE Applied Biosystems GeneAmp 5700 sequence detector was developed to detect infectious hypodermal and hematopoietic necrosis virus (IHHNV) in penaeid shrimp. A pair of PCR primers to amplify an 81 bp DNA fragment and a fluorogenic probe (TaqMan probe) were selected from ORF1 (open reading frame 1) of the IHHNV genome. The primers and TaqMan probe used in this assay were shown to be specific for IHHNV and did not react with either hepatopancreatic parvovirus (HPV), white-spot syndrome virus (WSSV), or shrimp DNA. A plasmid, pIHHNV-P4, containing the target IHHNV sequence was constructed and used as a positive control. The concentration of pIHHNV-P4 was determined through spectrophotometric analysis and the plasmid was used for quantitative studies. This real-time PCR assay had a detection limit of 10 copies and a log-linear range up to 5 x 10(7) copies of IHHNV DNA. The assay was then used to quantify IHHNV in infected shrimp collected from 5 locations: Hawaii, Panama, Mexico, Guam, and the Philippines. The quantitative analysis showed that wild-caught, large juvenile Penaeus stylirostris collected from the Gulf of California (Mexico) in 1996 were naturally infected with IHHNV and contained up to 10(9) copies of IHHNV microg(-1) of DNA. Similar quantities of IHHNV were detected in hatchery-raised, small juvenile P. stylirostris collected from Guam in 1995 and in farm-raised, post-larval P. monodon from the Philippines in 1996. Laboratory-infected P. stylirostris contained approximately 10(8) copies of IHHNV 31 d after being fed with IHHNV-infected shrimp tissue. In contrast, individuals of Super Shrimp, a line of P. stylirostris selected for IHHNV resistance, showed no signs of infection 32 d after ingesting IHHNV-infected shrimp tissue. Laboratory-infected P. vannamei also contained approximately 10(8) copies of IHHNV 30 d after being fed infected shrimp tissue. A time-course study of IHHNV replication in juvenile P. vannamei showed that the doubling time in the exponential growth phase was approximately 22 h.

A distinct expression of CC chemokines by macrophages in nasopharyngeal carcinoma: implication for the intense tumor infiltration by T lymphocytes and macrophages.

Nasopharyngeal carcinoma (NPC) is characterized by harboring Epstein-Barr virus genes in the tumor cells and an intense infiltration of leukocytes in the tumor tissue. These infiltrating cells are mainly composed of T lymphocytes and macrophages. The mechanism of this intense infiltration has long been a puzzle. We attempted to address this issue by studying the expression of CC chemokines, which are responsible for recruiting both T cells and macrophages, by an immunohistochemical approach. In biopsies obtained from nasopharynx of 17 NPC patients that contained tumor cells, expression of macrophage inflammatory protein 1alpha (MIP-1alpha), MIP-1beta, macrophage chemoattractant protein-1 (MCP-1), MCP-2, MCP-3, and RANTES was detected in the tumor-infiltrating cells, with MIP-1alpha and MCP-1 found in nearly all biopsies and the others relatively less frequently. Furthermore, expression of interferon-gamma (IFN-gamma) was also observed in tumor-infiltrating cells. In contrast, CC chemokines and IFN-gamma were rarely expressed in the 13 control biopsies that were either normal or with nonspecific inflammation, and in 4 biopsies from untreated NPC patients that contained no tumor cells. Using an immunofluorescent double-staining method, MIP-1alpha and MCP-1 were identified to be associated with macrophages, and IFN-gamma with T cells. Moreover, expression of CCR2 and CCR5, the receptors for these chemokines, was also detected in the tumor-infiltrating cells. These data indicate that the intense tumor infiltration by T cells and macrophages is a result of active recruitment. It seems possible that the intense infiltration of leukocytes in NPC tumor tissue is initiated by the activated tumor-reactive T cells. T cells migrate into the tumor tissue in an antigen-specific mode, and IFN-gamma secreted from these pioneer T cells activates tissue macrophages to express CC chemokines, especially MIP-1alpha and MCP-1, which consequently recruit more T cells and macrophages into the tumor tissue.

Increased production of interferon-gamma by tumour infiltrating T lymphocytes in nasopharyngeal carcinoma: indicative of an activated status.

Undifferentiated nasopharyngeal carcinomas (UNPC) are characterised by an association with Epstein-Barr virus and an abundant lymphoid stroma. We studied the functional status of the infiltrating T cells in ten UNPC biopsies using an immunohistochemical approach. Twelve non-NPC biopsies were included as controls. Tumour cells of UNPC were positive for HLA class I (10/10) and II (8/10), LMP1 (3/10), and CD86 (6/10). Tumour infiltrating T cells (TILs) were detected with antibodies directed at CD3, CD4, and CD8, and shown to be comparable to that in the control biopsies. Although expression of CD28 was shown to be decreased in TILs, expression of CD25 and IFN-gamma at a relatively high percentage could be consistently detected in the UNPC biopsies. These data suggest that TILs in UNPC are in an activated status, and this T cell response is possibly directed at the tumour cells.

A yellow head virus gene probe: nucleotide sequence and application for in situ hybridization.

A portion of the genome of yellow head virus (YHV) of penaeid shrimp was cloned and the cDNA fragment (1161 bp) was designated clone 3-27. The fragment was labeled with digoxigenin and hybridized in situ to tissue sections of YHV-infected Penaeus vannamei. Positively reacting tissues included those of the lymphoid organ, cuticular epithelium, and gills. In addition, connective tissue of hepatopancreas, heart, antennal gland, hematopoietic organ, nerve tract, midgut cecum and muscle reacted to the probe. The probe was highly specific since it hybridized only to tissues from YHV-infected shrimp. It did not react to those of uninfected shrimp or shrimp infected with WSSV (white spot syndrome virus), IHHNV (infectious hypodermal and hematopoietic necrosis virus), or TSV (Taura syndrome virus). The clone was sequenced, and primers were synthesized for rapid detection of YHV in hemolymph using RT-PCR (reverse transcription-polymerase chain reaction). The strand that constituted the viral sequence in the cDNA was also determined via RT-PCR and in situ hybridization with a single-stranded RNA (ssRNA) probe.

Identification and genetic characterization of yeasts isolated from freshwater prawns, Macrobrachium rosenbergii de Man, in Taiwan.

Since 1987, farmers in southern Taiwan have reported significant disease-related mortalities in freshwater prawns. Most mortalities have occurred during the winter, and usually almost all the adult prawns die within 4-5 days after clinical signs appear. Histopathological studies show that cells in hepatopancreatic ducts and tubules are vacuolized and degenerated. Large numbers of membrane-bound yeast aggregates are observed in the affected tissues. Two hundred and seventeen yeast isolates were obtained from diseased prawns, pond water and sediments from six areas. DNA restriction fragment length polymorphism (RFLP) was used to analyse the yeast genomes and to categorize them into five groups. Conventional biochemical and metabolic methods were then used to identify the yeasts of each group. The results showed that two strains of Candida sake (I and II), Pichia anomala, Endomyces fibuliger and Candida famata were present. In addition, the RAPD (random amplified polymorphic DNA) method was used to determine their genomic similarities. Two strains (I and II) of C. sake were the most similar (72%). C. sake I appears to be the primary causative agent of disease, based on frequencies of occurrence of the yeasts found in the diseased prawns.

Remission of Ménétrier's disease associated with ranitidine administration.

We describe a patient with Ménétrier's disease in whom acute administration of ranitidine reduced gastric protein loss more effectively than cimetidine or propantheline. This patient went into remission following a course of ranitidine. We reviewed the literature on remissions in Ménétrier's disease occurring without surgery. More detailed studies of various anti-secretory agents on individual patients are required to determine whether or not they are truly efficacious.

Production of interferon-beta upon induction with polyinosinic acid:polycytidylic acid during the cell cycle of human fibroblasts.

The production of interferon-beta was examined at various stages of the cell cycle in synchronized and unsynchronized cell populations induced by poly(I):poly(C). Human fibroblasts were synchronized with mitotic detachment and, at different stages of the cell cycle, poly(I):poly(C) was added for induction of interferon-beta. One hour after induction, cell-free medium was collected and assayed for secreted interferon-beta. The cells were then fixed and stained with a DNA-specific fluorochrome, 4',6-diamidino-2-phenylindole (DAPI), for cell cycle analysis by microfluorometry. The data indicated that interferon-beta was produced in every stage examined of the cell cycle. In addition, the level of intracellular interferon-beta was quantitatively measured in single cells of an unsynchronized cell population using a specific antibody. In the same individual cell, DAPI fluorescence intensity was measured for determination of the cell cycle position. The results show that interferon-beta protein can be detected throughout the cell cycle.

Nuclear medicine--an overview.

A radioactive isotope behaves chemically and biologically like its non-radioactive counterpart. The application of this principle to medical diagnosis has evolved into a whole specialty called nuclear medicine. The development of the rectilinear scanner and gamma camera has extended the study of molecular pathways into an exciting imaging modality while developments in radiopharmaceuticals have made radionuclide imaging of many organ systems widely available. The most significant improvements have occurred in bone, hepatobiliary and cardiac imaging. Today, however, nuclear medicine is evolving into a more dynamic study of physiological processes in the body and how these processes may be affected by disease and medical treatment. Emission tomography with a new generation of both gamma and positron emitters will be integral part of nuclear medicine in the future. The challenge to develop radio-labelled antibodies for immunotherapy and immunodetection remains while many of the older techniques like radioimmunoassay, and even the simple colloid liver scan, will continue to contribute significantly to health care.