TAK1-binding protein 2 (TAB2) and TAB3 are redundantly required for TLR-induced cytokine production in macrophages.

Transforming growth factor-ß-activated kinase 1 (TAK1) plays a pivotal role in innate and adaptive immunity. TAK1 is essential for the activation of mitogen-activated protein kinases (MAPKs) and nuclear factor (NF)-κB pathways downstream of diverse immune receptors, including toll-like receptors (TLRs). Upon stimulation with TLR ligands, TAK1 is activated via recruitment to the lysine 63-linked polyubiquitin chain through TAK1-binding protein 2 (TAB2) and TAB3. However, the physiological importance of TAB2 and TAB3 in macrophages is still controversial. A previous study has shown that mouse bone marrow-derived macrophages (BMDMs) isolated from mice double deficient for TAB2 and TAB3 produced tumor necrosis factor (TNF)-α and interleukin (IL)-6 to the similar levels as control wild-type BMDMs in response to TLR ligands such as lipopolysaccharide (LPS) or Pam3CSK4, indicating that TAB2 and TAB3 are dispensable for TLR signaling. In this study, we revisited the role of TAB2 and TAB3 using an improved mouse model. We observed a significant impairment in the production of pro-inflammatory cytokines and chemokine in LPS- or Pam3CSK4-treated BMDMs deficient for both TAB2 and TAB3. Double deficiency of TAB2 and TAB3 resulted in the decreased activation of NF-κB and MAPK pathways as well as the slight decrease in TAK1 activation in response to LPS or Pam3CSK4. Notably, the TLR-mediated expression of inhibitor of NF-κB (IκB)ζ was severely compromised at the protein and messenger RNA (mRNA) levels in the TAB2/TAB3 double-deficient BMDMs, thereby impeding IL-6 production. Our results suggest that TAB2 and TAB3 play a redundant and indispensable role in the TLR signaling pathway.

First monitoring of resistance and corresponding mechanisms in the green peach aphid, Myzus persicae (Sulzer), to registered and unregistered insecticides in Saudi Arabia.

Insecticides are widely used as the primary management strategy for controlling Myzus persicae, the devastating pest ravaging various vegetables, fruits, crops, and ornamentals. This study examined the susceptibility of M. persicae field populations to bifenthrin, fosthiazate, acetamiprid, spirotetramat, afidopyropen, and flonicamid while exploring the possible metabolic mechanisms of resistance. The study findings revealed that M. persicae field populations exhibited susceptible-to-moderate resistance to bifenthrin (resistance ratio (RR) = 0.94-19.65) and acetamiprid (RR = 1.73-12.91), low-to-moderate resistance to fosthiazate (RR = 3.67-17.00), and susceptible-to-low resistance to spirotetramat (RR = 0.70-6.68). However, all M. persicae field populations were susceptible to afidopyropen (RR = 0.44-2.25) and flonicamid (RR = 0.40-2.08). As determined by the biochemical assays, carboxylesterases were involved in the resistance cases to bifenthrin and fosthiazate, whereas cytochrome P450 monooxygenases were implicated in the resistance cases to acetamiprid. However, glutathione S-transferases were not implicated in the documented resistance of M. persicae field populations. Overall, the susceptibility of M. persicae field populations to flonicamid and afidopyropen-two unregistered insecticides in Saudi Arabia-suggests their potential as promising chemicals that can expand the various alternatives available for controlling this devastating pest. Although the detected moderate levels of resistance to bifenthrin, fosthiazate, and acetamiprid indicate a shift in the selection pressure of insecticides for M. persicae due to Saudi regulations, which have resulted in eventual obsolescence of conventional insecticides in favor of novel insecticides. Finally, rotational use of aforementioned insecticides can help in managing insecticide resistance in M. persicae.

Community composition, bacterial symbionts, antibacterial and antioxidant activities of honeybee-associated fungi.

BACKGROUND: Fungi associated with insects represent one potentially rich source for the discovery of novel metabolites. However, a comprehensive understanding of the fungal communities of Apis mellifera ligustica remains elusive. RESULTS: Here, we investigated the phylogenetic diversity and community composition of honeybee-associated fungi using combination of culture-dependent and culture-independent approaches. A total of forty-five fungi were isolated and purified from the Apis mellifera ligustica, royal jelly, and honeycomb, which belonged to four classes and eleven different genera. Furthermore, 28 bacterial 16S rRNA gene sequences were obtained by PCR from the fungal metagenome. High-throughput sequencing analyses revealed that the fungal communities were more diverse, a total of 62 fungal genera were detected in the honeybee gut by culture-independent method, whereas only 4 genera were isolated by culture-dependent method. Similarly, 247 fungal genera were detected in the honeycomb, whereas only 4 genera were isolated. In addition, we assessed the antibacterial and antioxidant activities of fungal isolates. Most fungal crude extracts obtained from the cultivation supernatant exhibited antioxidant activities. Only two fungal crude extracts displayed moderate activity against Escherichia coli and Staphylococcus aureus. Chemical analysis of Chaetomium subaffine MFFC22 led to the discovery of three known compounds, including cochliodinol (1), emodin (2), chrysophanol (3). Among them, cochliodinol (1) showed intense DPPH radical scavenging activity with the 50% inhibitory concentration (IC50) of 3.06 µg/mL, which was comparable to that of the positive ascorbic acid (IC50 = 2.25 µg/mL). Compound 2 displayed weak inhibitory activities against Micrococcus tetragenus and S. aureus. CONCLUSIONS: This research provided a fundamental clue for the complex interactions among honeybees, fungi, bacterial symbionts, and the effects on the honeybee. Furthermore, the diversity of honeybee-associated fungi had great potential in finding the resource of new species and antioxidants.

Monitoring of field-evolved resistance to flonicamid, neonicotinoid, and conventional insecticides in the Oxycarenus hyalinipennis costa.

Oxycarenus hyalinipennis Costa is a polyphagous insect pest and can develop insecticide resistance. The resistance of O. hyalinipennis to neonicotinoids (clothianidin and dinotefuran), flonicamid, and conventional insecticides; carbamates (methomyl and carbosulfon), organophosphates (chlorpyrifos and malathion), and pyrethroids (cypermethrin and zeta-cypermethrin) was evaluated. The O. hyalinipennis populations were sampled from four locations in Pakistan and performed bioassays against the insecticides by leaf dip protocol. The O. hyalinipennis' populations showed low resistance to carbosulfan (resistance ratio (RR) = 2.06-6.34) and methomyl (RR = 2.78-7.27), moderate to high resistance to chlorpyrifos (RR = 30-45), malathion (RR = 20.29-88.19), and flonicamid (RR = 14.24-46.97), in comparison with the susceptible strain. Susceptibility to low resistance against cypermethrin (RR = 1.27-2.82), zeta-cypermethrin (RR = 2.62-3.38), and clothianidin (RR = 1.74-3.40), and low to moderate resistance to dinotefuran (RR = 3.84-13.43) in the field populations, was observed compared to the susceptible strain. A rotational usage of carbamates and pyrethroids with an integrated pest management tool should be considered to deal with O. hyalinipennis' insecticide resistance.

Symmetrical aryl linked bis-iminothiazolidinones as new chemical entities for the inhibition of monoamine oxidases: Synthesis, in vitro biological evaluation and molecular modelling analysis.

The multifactorial nature of Parkinson's disease necessitates the development of new chemical entities with inherent ability to address key pathogenic processes. To this end, two series of new symmetrical 1,2- and 1,4-bis(2-aroyl/alkoylimino-5-(2-methoxy-2-oxoethylidene)-4-oxo-thiazolidin-3-yl)benzene derivatives (3a-g and 5a-e) were synthesized in good yields by the cyclization of 1,2- and 1,4-bis(N'-substituted thioureido)benzene intermediates with dimethyl acetylenedicarboxylate (DMAD) in methanol at ambient temperature. The bis-iminothiazolidinone compounds were investigated in vitro for their inhibition of monoamine oxidase (MAO-A & MAO-B) enzymes with the aim to identify new and distinct pharmacophores for the treatment of neurodegenerative disorders like Parkinson's disease. Most of the designed compounds exhibited good inhibitory efficacy against monoamine oxidases. Compound 5a was identified as the most potent inhibitor of MAO-A depicting an IC50 value of 0.001µM, a 4-fold stronger inhibitory strength compared to standard inhibitor (clorgyline: IC50=0.0045µM). Molecular docking studies provided insights into enzyme-inhibitor interactions and a rationale for the observed inhibition towards monoamine oxidases.

Resistance of green lacewing, Chrysoperla carnea Stephens to nitenpyram: Cross-resistance patterns, mechanism, stability, and realized heritability.

The green lacewing, Chrysoperla carnea Stephens (Neuroptera: Chrysopidae) is a major generalist predator employed in integrated pest management (IPM) plans for pest control on many crops. Nitenpyram, a neonicotinoid insecticide has widely been used against the sucking pests of cotton in Pakistan. Therefore, a field green lacewing strain was exposed to nitenpyram for five generations to investigate resistance evolution, cross-resistance pattern, stability, realized heritability, and mechanisms of resistance. Before starting the selection with nitenpyram, a field collected strain showed 22.08-, 23.09-, 484.69- and 602.90-fold resistance to nitenpyram, buprofezin, spinosad and acetamiprid, respectively compared with the Susceptible strain. After continuous selection for five generations (G1-G5) with nitenpyram in the laboratory, the Field strain (Niten-SEL) developed a resistance ratio of 423.95 at G6. The Niten-SEL strain at G6 showed no cross-resistance to buprofezin and acetamiprid and negative cross-resistance to spinosad compared with the Field strain (G1). For resistance stability, the Niten-SEL strain was left unexposed to any insecticide for four generations (G6-G9) and bioassay results at G10 showed that resistance to nitenpyram, buprofezin and spinosad was stable, while resistance to acetamiprid was unstable. The realized heritability values were 0.97, 0.16, 0.03, and -0.16 to nitenpyram, buprofezin, acetamiprid and spinosad, respectively, after five generations of selection. Moreover, the enzyme inhibitors (PBO or DEF) significantly decreased the nitenpyram resistance in the resistant strain, suggesting that resistance was due to microsomal oxidases and esterases. These results are very helpful for integration of green lacewings in IPM programs.

Quinazolines and quinazolinones as ubiquitous structural fragments in medicinal chemistry: An update on the development of synthetic methods and pharmacological diversification.

Nitrogen-rich heterocycles, particularly quinazolines and quinazolinones, represent a unique class of diversified frameworks displaying a broad spectrum of biological functions. Over the past several years, intensive medicinal chemistry efforts have generated numerous structurally functionalized quinazoline and quinazolinone derivatives. Interest in expanding the biological effects, demonstrated by these motifs, is growing exponentially, as indicated by the large number of publications reporting the easy accessibility of these skeletons in addition to the diverse nature of synthetic as well as biological applications. Therefore, the main focus of the present review is to provide an ample but condensed overview on various synthetic approaches providing access to quinazoline and quinazolinone compounds with multifaceted biological activities. Furthermore, mechanistic insights, synthetic utilization, structure-activity relationships and molecular modeling inputs for the potent derivatives have also been discussed.

Biological trait analysis and stability of lambda-cyhalothrin resistance in the house fly, Musca domestica L. (Diptera: Muscidae).

House flies, Musca domestica L., (Diptera: Muscidae), are pests of poultry and have the ability to develop resistance to insecticides. To design a strategy for resistance management, life history traits based on laboratory observations were established for lambda-cyhalothrin-resistant, susceptible and reciprocal crosses of M. domestica strains. Bioassay results showed that the lambda-cyhalothrin-selected strain developed a resistance ratio of 98.34 compared to its susceptible strain. The lambda-cyhalothrin-selected strain had a relative fitness of 0.26 and lower fecundity, hatchability, lower number of next generation larvae, and net reproductive rate compared with its susceptible strain. Mean population growth rates, such as intrinsic rate of population increase, and biotic potential were lower for the lambda-cyhalothrin-selected strain compared to its susceptible strain. Resistance to lambda-cyhalothrin, indoxacarb, and abamectin was unstable while resistance to bifenthrin and methomyl was stable in the lambda-cyhalothrin-selected strain of M. domestica. Development of resistance can cost considerable fitness for the lambda-cyhalothrin-selected strain. The present study provided useful information for making potential management strategies to delay resistance development in M. domestica.

Resistance of Dusky Cotton Bug, Oxycarenus hyalinipennis Costa (Lygaidae: Hemiptera), to Conventional and Novel Chemistry Insecticides.

The dusky cotton bug, Oxycarenus hyalinipennis Costa (Lygaidae: Hemiptera), is polyphagous in nature and has become one of the severe sucking pests of cotton in Pakistan. O. hyalinipennis has the potential to develop resistance to a number of insecticides, and as a result, O. hyalinipennis outbreaks occur. There is no previous study from Pakistan regarding O. hyalinipennis resistance to insecticides. Therefore, the aim of this study was to assess the resistance of different field populations of O. hyalinipennis to conventional (bifenthrin, deltamethrin, lambda-cyhalothrin, profenofos, triazophos) and novel chemistry (emamectin benzoate, spinosad, chlorfenapyr, imidacloprid, and nitenpyram) insecticides. Five populations of O. hyalinipennis, collected from Multan, Khanewal, Muzaffargarh, Lodhran, and Bahawalpur, were tested for resistance to selected insecticides by the leaf dip method. For three pyrethroids, the resistance ratios were in the range of 14- to 30-fold for bifenthrin, 2.14- to 8.41-fold for deltamethrin, and 9.12- to 16-fold for lambda-cyhalothrin, compared with the laboratory susceptible strain (Lab-PK). For two organophosphates, the range of resistance ratios was 12- to 14-fold for profenofos and 9.04- to 15-fold for triazophos. For five novel chemistry insecticides, the range of resistance ratios was 4.68- to 9.83-fold for emamectin benzoate, 6.38- to 17-fold for spinosad, 16- to 46-fold for chlorfenapyr, 11- to 22-fold for imidacloprid, and 1.32- to 11-fold for nitenpyram. Regular assessment of resistance to insecticides and integrated management plans like judicious use of insecticides and rotation of insecticides along with different modes of action are required to delay resistance development in O. hyalinipennis.

Genetics, realized heritability and preliminary mechanism of spinosad resistance in Phenacoccus solenopsis Tinsley (Homoptera: Pseudococcidae): an invasive pest from Pakistan.

The cotton mealybug, Phenacoccus solenopsis Tinsley (Homoptera: Pseudococcidae) has gained recognition as a key pest due to its invasive nature throughout the world. The P. solenopsis has a wide range of host plants and damages the cotton crop in various parts of the world. In view of the economic importance of this pest, a study on selection, inheritance and mechanism of spinosad resistance was conducted on P. solenopsis. Selection of field collected P. solenopsis for seven generations with spinosad resulted in a high resistance ratio of 282.45-fold. Genetic studies of spinosad resistance in P. solenopsis indicated that maternal effects are not involved in spinosad resistance; and resistance development is an autosomal and incompletely dominant trait. The number of genes involved in spinosad resistance was determined to be more than one, suggesting that resistance is controlled by multiple loci. The realized heritability (h (2)) value for spinosad resistance was 0.94. Synergism bioassays of spinosad with piperonyl butoxide and S,S,S-tributyl phosphorotrithioate showed that spinosad resistance in P. solenopsis could be due to esterase only. The study provides the basic information for implementation of effective resistance management strategies to control P. solenopsis.

Assessment of resistance risk to lambda-cyhalothrin and cross-resistance to four other insecticides in the house fly, Musca domestica L. (Diptera: Muscidae).

Lambda-cyhalothrin, a sodium channel modulator insecticide, has been used frequently for the control of house flies, Musca domestica L. (Diptera: Muscidae) worldwide, including Pakistan. This experiment was performed to determine the selection and assessment of lambda-cyhalothrin resistance evolution along with four other insecticides. After 26 generations of selection, the lambda-cyhalothrin-selected population developed 445-fold resistance to lambda-cyhalothrin compared to the susceptible population. There was low cross-resistance to bifenthrin and very low cross-resistance to methomyl, imidacloprid, and fipronil in the lambda-cyhalothrin-selected population compared to the field population (G1). Realized heritability (h (2)) of resistance to lambda-cyhalothrin, bifenthrin, methomyl, imidacloprid, and fipronil was 0.07, 0.05, 0.01, 0.08, and 0.08, respectively. The projected rate of resistance development revealed that if 90 % house flies were selected, then a tenfold increase in lethal concentration 50 occurred after 17, 20, 159, 13, and 14 generations for lambda-cyhalothrin (h (2) = 0.07, slope = 2.09), bifenthrin (h (2) = 0.05, slope = 1.73), methomyl (h (2) = 0.01, slope = 2.52), imidacloprid (h (2) = 0.08, slope = 1.89), and fipronil (h (2) = 0.08, slope = 2.03), respectively. The results of our study concluded that the house fly has the potential to develop multiple insecticide resistances following continued selection pressure with lambda-cyhalothrin. This study will be helpful for assisting the development of resistance management strategies.

Cross-resistance, stability, and fitness cost of resistance to imidacloprid in Musca domestica L., (Diptera: Muscidae).

Imidacloprid, a neonicotinoid insecticide, has been used frequently for the management of Musca domestica L., (Diptera: Muscidae) worldwide. To design the strategy for resistance management, life history traits were established for imidacloprid-resistant, susceptible counterpart, and reciprocal crosses M. domestica strains based on laboratory observations. Bioassay results showed that the imidacloprid-selected strain developed a resistance ratio of 106-fold to imidacloprid, 19-fold to nitenpyram, 29-fold to chlorpyrifos, and 3.8-fold to cypermethrin compared to that of the susceptible counterpart strain. The imidacloprid-selected strain showed very low cross-resistance against nitenpyram and cypermethrin and a lack of cross-resistance to chlorpyrifos. Resistance to imidacloprid, nitenpyram, and chlorpyrifos was unstable, while resistance to cypermethrin was stable in Imida-SEL strain of M. domestica. The imidacloprid-selected strain had a relative fitness of 0.61 and lower fecundity, hatchability, number of next-generation larvae, and net reproductive rate compared with the susceptible counterpart strain. Mean population growth rates, such as intrinsic rate of population increase and biotic potential, were lower for the imidacloprid-selected strain compared with the susceptible counterpart strain. Development of resistance can cost considerable fitness for the imidacloprid-selected strain. The present study provided useful information for making potential management strategies to overcome development of resistance.

Selection, resistance risk assessment, and reversion toward susceptibility of pyriproxyfen in Musca domestica L.

Pyriproxyfen, a juvenile hormone mimic, is an effective larvicide against many pests of veterinary and public health importance. Pyriproxyfen is a biorational insecticide having many environmentally friendly attributes that make it compatible with integrated pest management programs. This experiment was performed for the assessment of resistance evolution and reversion toward susceptibility of Musca domestica to pyriproxyfen. Repeated selection at successive generations resulted in 5.09- and 130-fold increase in lethal concentration 50 (LC50) compared to field and susceptible strain, respectively. A significant decline after 22 generations without selection suggesting resistance to pyriproxyfen was unstable in M. domestica. Realized heritability (h (2)) of resistance to pyriproxyfen was 0.035 in pyriproxyfen-selected strain of M. domestica. The projected rate of resistance development indicated that, if slope = 1.28 and h (2) = 0.035, then 46-21 generations are required for 10-fold increase in LC50 at 50-90 % selection intensity. These findings suggest that a risk for resistance development to pyriproxyfen occurred in M. domestica under continuous selection pressure. Pyriproxyfen susceptibility reversed when its application is ceased for a specified duration.

Inheritance, realized heritability and biochemical mechanism of acetamiprid resistance in the cotton mealybug, Phenacoccus solenopsis Tinsley (Homoptera: Pseudococcidae).

The cotton mealybug, Phenacoccus solenopsis Tinsley (Homoptera: Pseudococcidae) is a serious pest in many countries of the world because of its polyphagous nature and has caused huge losses to the cotton crop. The aim of present study was to explore the mode of inheritance and mechanism of acetamiprid resistance in P. solenopsis. After five rounds of selection with acetamiprid, P. solenopsis developed a 315-fold resistance compared with the laboratory susceptible population. The LC50 values of progenies of both reciprocal crosses (F1 and F1') showed no significant difference and degree of dominance values were 0.56 and 0.93 for F1 and F1', respectively. Monogenic model of inheritance and Lande's method revealed that more than one factors were involved in acetamiprid resistance. Realized heritability (h(2)) value was 0.58 for acetamiprid resistance. A synergism study of piperonyl butoxide (PBO) and S,S,S-tributylphosphorotrithioate (DEF) with acetamiprid also showed the significant presence of P-450 mono-oxygenase and esterase in the acetamiprid resistance. Hence, acetamiprid resistance in the P. solenopsis was autosomal, incompletely dominant and polygenic. These results are a source of basic information to design and plan fruitful management programmes to control P. solenopsis.

Mechanism, stability and fitness cost of resistance to pyriproxyfen in the house fly, Musca domestica L. (Diptera: Muscidae).

Pyriproxyfen, a bio-rational insecticide, used worldwide for the management of many insect pests including the house fly, Musca domestica. To devise a retrospective resistance management strategy, biological parameters of pyriproxyfen resistant (Pyri-SEL), unselected (UNSEL), Cross1 and Cross2M. domestica strains were studied in the laboratory. Additionally, the stability and mechanism of resistance was also investigated. After 30 generations of pyriproxyfen selection, a field-collected strain developed 206-fold resistance compared with susceptible strain. Synergists such as piperonyl butoxide and S,S,S-tributylphosphorotrithioate did not alter the LC50 values, suggesting another cause of target site resistance to pyriproxyfen in the Pyri-SEL strain. The resistance to all tested insecticides was unstable in Pyri-SEL strain. The relative fitness of 0.51 with lower fecundity, hatchability, lower number of next generation larvae, reduced mean population growth rate and net reproductive rate were observed in the Pyri-SEL strain compared with the UNSEL strain. The cost of fitness associated with pyriproxyfen resistance was evident in Pyri-SEL strain. The present study provides useful information for making pro-active resistance management strategies to delay resistance development.

Genetics and preliminary mechanism of chlorpyrifos resistance in Phenacoccus solenopsis Tinsley (Homoptera: Pseudococcidae).

Cotton mealybug, Phenacoccus solenopsis Tinsley, is a serious pest of cotton and other crops and infestation by this pest results in yield losses that affect the economy of Pakistan. Various groups of insecticides have been used to control this pest but resistance development is a major factor that inhibits its control in the field. Chlorpyrifos is a common insecticide used against many pests including P. solenopsis. The present experiment was designed to assess the genetics and mechanism of chlorpyrifos resistance and to develop a better resistance management strategy and assess the genetics and mechanism of chlorpyrifos resistance. Before selection, the field strain showed 3.1-fold resistance compared to the susceptible strain (CSS). After 8 rounds of selection with chlorpyrifos, a selected population developed a 191.0-fold resistance compared to the CSS. The LC50 values of F1 (CRR ♀ × CSS ♂) and F1(†) (CRR ♂ × CSS ♀) strains were not significantly different and dominance (DLC) values were 0.42 and 0.55. Reciprocal crosses between chlorpyrifos susceptible and resistant strains indicated that resistance was autosomal and incompletely recessive. The monogenic model of fit test and calculation of number of genes segregating in the chlorpyrifos resistant strain demonstrated that resistance is controlled by multiple genes. A value of 0.59 was calculated for realized heritability for chlorpyrifos resistance. Synergism bioassays with piperonyl butoxide and S, S, S-butyl phosphorotrithioate showed that chlorpyrifos resistance was associated with microsomal oxidases and esterases. It was concluded that chlorpyrifos resistance in P. solenopsis was autosomally inherited, incompletely recessive and polygenic. These findings would be helpful to improve the management of P. solenopsis.

Resistance to Conventional and New Insecticides in House Flies (Diptera: Muscidae) From Poultry Facilities in Punjab, Pakistan.

House flies, Musca domestica L., are pests of poultry facilities and have the ability to develop resistance against different insecticides. This study was conducted to assess the resistance status of house flies to pyrethroid, organophosphate, and novel chemistry insecticides from poultry facilities in Punjab, Pakistan. Five adult house fly populations were studied for their resistance status to selected conventional and novel chemistry insecticides. For four pyrethroids, the range of resistance ratios was 14-55-fold for cypermethrin, 11-45-fold for bifenthrin, 0.84-4.06-fold for deltamethrin, and 4.42-24-fold for lambda-cyhalothrin when compared with a susceptible population. Very low levels of resistance were found to deltamethrin compared with the other pyrethroids. For the three organophosphate insecticides, the range of resistance ratios was 1.70-16-fold for profenofos, 7.50-60-fold for chlorpyrifos, and 4.37-53-fold for triazophos. Very low levels of resistance were found to profenofos compared with the other insecticides. For five novel chemistry insecticides, the range of resistance ratios was 1.20-16.00-fold for fipronil, 3.73-7.16-fold for spinosad, 3.06-23-fold for indoxacarb, 0.96-5.88-fold for abamectin, and 0.56-3.07-fold for emamectin benzoate. Rotation of insecticides with different modes of action showing no or very low resistance may prevent insecticide resistance in house flies. Regular insecticide resistance monitoring and integrated management plans on poultry farms are required to prevent resistance development, field control failures, and environmental pollution.

Prognostic significance of hypokalemia in hepatic encephalopathy.

BACKGROUND/AIMS: The aim of this study was to investigate whether hypokalemia prognosticates outcomes in hepatic encephalopathy. We also examined other potential prognostic variables such as serum pH, systemic vascular resistance (SVR) and serum ammonia levels. METHODOLOGY: Patients with cirrhosis who were admitted for overt hepatic encephalopathy were included in the study and divided into two groups: Group-I consisted of patients with serum Potassium level < 4.0 mEq/L and Group-II consisted of patients with serum Potassium level > 4.0 mEq/L. We collected the baseline demographic data for both the groups including age, gender, ethnicity and calculated the Model for End Stage Liver Disease scores for both the groups at the time of admission. We analyzed the correlation between serum potassium levels and outcome variables including 30- day mortality rate, length of Intensive Care Unit (ICU)/ hospital stay, mechanical ventilation rate and 30-day readmission rate. RESULTS: A total of 447 patients with diagnosis of cirrhosis were admitted to the hospital with overt hepatic encephalopathy between January 2008 and December 2012. 157 patients with low Potassium level (< 4.0 mEq/L) were included in Group-I while 290 patients with normal Potassium level (> 4.0 mEq/L) and were included in Group-II. Total length of stay in the hospital (P Value= 0.0001) and ICU length of stay (P Value= 0.0003) were significantly longer among the patients with serum potassium level of <4mEq/L. CONCLUSIONS: We observed statistically significant correlation between serum potassium level and length of stay in hospital and ICU.

Cross-resistance, genetics, and realized heritability of resistance to fipronil in the house fly, Musca domestica (Diptera: Muscidae): a potential vector for disease transmission.

Houseflies, Musca domestica (L.), are ubiquitous pests that have the potential to spread a variety of pathogens to humans, poultries, and dairies. Pesticides are commonly used for the management of this pest. Fipronil is a GABA-gated chloride channel-inhibiting insecticide that has been commonly used for the management of different pests including M. domestica throughout the world. Many pests have developed resistance to this insecticide. A field-collected strain of M. domestica was selected with fipronil for continuous 11 generations to assess the cross-resistance, genetics, and realized heritability for designing a resistance management strategy. Laboratory bioassays were performed using the feeding method of mixing insecticide concentrations with 20% sugar solutions and cotton soaks dipped in insecticide solutions were provided to tested adult flies. Bioassay results at G12 showed that the fipronil-selected strain developed a resistance ratio of 140-fold compared to the susceptible strain. Synergism bioassay with piperonyl butoxide (PBO) and S,S,S,-tributyl phosphorotrithioate (DEF) indicated that fipronil resistance was associated with microsomal oxidase and also esterase. Reciprocal crosses between resistant and susceptible strains showed an autosomal and incompletely dominant resistance to fipronil. The LC50 values of F1 and F'1 strains were not significantly different and dominance values were 0.74 and 0.64, respectively. The resistance to fipronil was completely recessive (D(ML) = 0.00) at the highest dose and incompletely dominant at the lowest dose (D(ML) = 0.87). The monogenic resistance based on chi-square goodness of fit test and calculation of the minimum number of segregating genes showed that resistance to fipronil is controlled by multiple genes. The fipronil resistance strain confirmed very low cross-resistance to emamectin benzoate and spinosad while no cross-resistance to chlorpyrifos and acetamiprid when compared to that of the field population. The heritability values were 0.112, 0.075, 0.084, 0.008, and 0.052 for fipronil, emamectin benzoate, spinosad, acetamiprid, and chlorpyrifos, respectively. It was concluded that fipronil resistance in M. domestica was autosomally inherited, incompletely dominant, and polygenic. These findings would be helpful for the better and successful management of M. domestica.