Formulation and evaluation of miconazole lipogel for enhanced drug permeation.

Hydrophilic drugs could be incorporated into the skin surface by manes of Lipogel. This study aimed to prepare miconazole lipogel with natural ingredients to enhance drug permeability using dimethyl Sulfoxide (DMSO). The miconazole lipogels, A1 (without DMSO) and A2 (with DMSO) were formulated and evaluated for organoleptic evaluation, pH, viscosity, stability studies, freeze-thawing, drug release profile and drug permeation enhancement. Results had stated that prepared lipogel's pH falls within the acceptable range required for topical delivery (4 to 6) while both formulations show good results in organoleptic evaluation. The A2 formulation containing DMSO shows better permeation of miconazole (84.76%) on the artificial skin membrane as compared to A1 lipogel formulation (50.64%). In in-vitro drug release studies, A2 for-mulation showed 87.48% drug release while A1 showed just 60.1% drug release from lipogel. Stability studies were performed on model formulations under environmental conditions and both showed good spreadibility, stable pH, free of grittiness and good consistency in formulation. The results concluded that A2 formulation containing DMSO shows better results as compared to DMSO-free drug lipogel.

Safety Considerations for Lyophilized Human Amniotic Membrane Impregnated with Colistin and Silver Nanoparticles.

Lyophilized human amniotic membrane (HAM) and silver nanoparticles (AgNPs) have multispectral applications as a biological dressing. The present study focuses on the safety aspects of HAM coated with colistin and AgNPs (HACoN) dressing in relation to its structural and hematological changes. Four dressing groups were designed for the study, HAM, HAM coated with colistin (HACo), HAM coated with AgNPs (HAN), and HAM coated with colistin (HACo) and HACoN. Scanning electron microscopy (SEM) and Fourier-transform infrared spectroscopy (FTIR) were utilized for constitutional analysis. Biological safety was checked by applying HAM of all groups on open excisional burn wounds on Sprague-Dawley rats for 21 days. The skin, kidneys, liver, and spleen were removed, and histological analysis was performed for detailed structural analysis. Oxidative stress was assessed using homogenate from newly generated skin. No structural or biochemical change was observed in any of the study groups as observed by SEM and FTIR. After 21 days of grafting, wounds were healed properly with normal skin, and no anomaly was observed in related to kidneys, spleen, and liver. Some of antioxidant enzymes were increased, while malondialdehyde which is a reactive oxygen species was reduced in the skin tissue homogenate of HACoN group. Impregnation of colistin and AgNPs in combination on HAM has no effects on hematological and structural constitution of HAM. It leaves no obvious change in vital organs of rats and improves oxidative stress and inflammation. Hence, it can be claimed that HACoN is a biologically safe antibacterial dressing.

Single-fly assemblies fill major phylogenomic gaps across the Drosophilidae Tree of Life.

Long-read sequencing is driving rapid progress in genome assembly across all major groups of life, including species of the family Drosophilidae, a longtime model system for genetics, genomics, and evolution. We previously developed a cost-effective hybrid Oxford Nanopore (ONT) long-read and Illumina short-read sequencing approach and used it to assemble 101 drosophilid genomes from laboratory cultures, greatly increasing the number of genome assemblies for this taxonomic group. The next major challenge is to address the laboratory culture bias in taxon sampling by sequencing genomes of species that cannot easily be reared in the lab. Here, we build upon our previous methods to perform amplification-free ONT sequencing of single wild flies obtained either directly from the field or from ethanol-preserved specimens in museum collections, greatly improving the representation of lesser studied drosophilid taxa in whole-genome data. Using Illumina Novaseq X Plus and ONT P2 sequencers with R10.4.1 chemistry, we set a new benchmark for inexpensive hybrid genome assembly at US $150 per genome while assembling genomes from as little as 35 ng of genomic DNA from a single fly. We present 183 new genome assemblies for 179 species as a resource for drosophilid systematics, phylogenetics, and comparative genomics. Of these genomes, 62 are from pooled lab strains and 121 from single adult flies. Despite the sample limitations of working with small insects, most single-fly diploid assemblies are comparable in contiguity (>1Mb contig N50), completeness (>98% complete dipteran BUSCOs), and accuracy (>QV40 genome-wide with ONT R10.4.1) to assemblies from inbred lines. We present a well-resolved multi-locus phylogeny for 360 drosophilid and 4 outgroup species encompassing all publicly available (as of August 2023) genomes for this group. Finally, we present a Progressive Cactus whole-genome, reference-free alignment built from a subset of 298 suitably high-quality drosophilid genomes. The new assemblies and alignment, along with updated laboratory protocols and computational pipelines, are released as an open resource and as a tool for studying evolution at the scale of an entire insect family.

Evolution of NLR genes in genus Arachis reveals asymmetric expansion of NLRome in wild and domesticated tetraploid species.

Arachis hypogaea is an allotetraploid crop widely grown in the world. Wild relatives of genus Arachis are the rich source of genetic diversity and high levels of resistance to combat pathogens and climate change. The accurate identification and characterization of plant resistance gene, nucleotide binding site leucine rich repeat receptor (NLRs) substantially contribute to the repertoire of resistances and improve production. In the current study, we have studied the evolution of NLR genes in genus Arachis and performed their comparative genomics among four diploids (A. duranensis, A. ipaensis, A. cardenasii, A. stenosperma) and two tetraploid (wild: A. monticola and domesticated: A. hypogaea) species. In total 521, 354, 284, 794, 654, 290 NLR genes were identified from A. cardenasii, A. stenosperma and A. duranensis, A. hypogaea, A. monticola and A. ipaensis respectively. Phylogenetic analysis and classification of NLRs revealed that they belong to 7 subgroups and specific subgroups have expanded in each genome leading towards divergent evolution. Gene gain and loss, duplication assay reveals that wild and domesticated tetraploids species have shown asymmetric expansion of NLRome in both sub-genome (AA and BB). A-subgenome of A. monticola exhibited significant contraction of NLRome while B-subgenome shows expansion and vice versa in case of A. hypogaea probably due to distinct natural and artificial selection pressure. In addition, diploid species A. cardenasii revealed the largest repertoire of NLR genes due to higher frequency of gene duplication and selection pressure. A. cardenasii and A. monticola can be regarded as putative resistance resources for peanut breeding program for introgression of novel resistance genes. Findings of this study also emphasize the application neo-diploids and polyploids due to higher quantitative expression of NLR genes. To the best of our knowledge, this is the first study that studied the effect of domestication and polyploidy on the evolution of NLR genes in genus Arachis to identify genomic resources for improving resistance of polyploid crop with global importance on economy and food security.

Evaluation of pain experienced by orthodontic patients following elastomeric separator insertion: A cross-sectional study / 대한치과교정학회지

Objective@#Pain following the insertion of separators and archwires varies with age, sex, race, ethnicity, threshold, and health status. This study aimed to evaluate the characteristics of pain in orthodontic patients after the insertion of elastomeric separators, its effects on daily life, and its association with age and sex in a population not previously studied in this regard. @*Methods@#A crosssectional study of 130 patients undergoing orthodontic treatment included collecting data on demographics, pain experienced following the placement of separators, time of onset, duration, characteristics, change in dietary pattern or chewing side, intake of analgesics, and severity of pain on the Wong Baker’s scale. The results are reported as counts and percentages. Associations between sex and age were evaluated using Pearson’s chi-square test. @*Results@#Among the 130 patients, 56.2% were 9–20 years old, 63.8% experienced pain following the insertion of separators, 22.9% had their first episode of pain at 4 hours, 56.6% experienced intermittent pain, and 37.3% experienced discomfort; 18.1% males and 81.9% females experienced pain following the insertion of separators.Pearson’s chi-square test showed a significant association between pain and sex (P = 0.04). Most patients (37.3%) reported “hurts little more” for pain intensity on Wong Baker’s scale and 21.7% reported all four quadrants as sites of pain. @*Conclusions@#The pain experienced after separator insertion was associated with sex and age. Females experienced more pain than males and patients between the age range of 21 and 36 years suffered more pain during mastication than between 9 and 20 years old.

Investigation of the Antibacterial, Anti-Biofilm, and Antioxidative Effect of Piper betle Leaf Extract against Bacillus gaemokensis MW067143 Isolated from Dental Caries, an In Vitro-In Silico Approach.

Among oral diseases, dental caries is one of the most frequent to affect human health. The current research work aimed to ascertain the antibacterial, anti-biofilm, and antioxidative potential of Piper betle leaf extract against bacteria isolated from dental caries. Analysis for the presence of phytochemical compounds revealed compounds, such as tannins, steroids, phenolic compounds, and alkaloids, which were also confirmed by TLC and FTIR. GC-MS analysis elucidated the presence of 20 phytocompounds, among which were some well-reported bioactive compounds. The chloroform extract of P. betle demonstrated good antibacterial activity (7 mm) and minimum inhibitory concentration (MIC) (100 mg mL-1) against Bacillus gaemokensis MW067143, which was the frequent biofilm producer among isolated bacterial strains. Fractions of the extract were isolated through column chromatography, after which the antibacterial activity was again evaluated. Spirost-8-en-11-one,3-hydroxy(3ß,5α,14ß,20ß,22ß,25R), an oxosteroid in nature, was observed to exhibit remarkable antibacterial potential (12 mm) against B. gaemokensis. Bacterial cells treated with P. betle extract had elevated SOD, APOX, POX, and GR activity, while its proteolytic activity against whole bacterial proteins was pronounced with the suppression of several proteins (50, 40, 15, and 10 kDa) in SDS-PAGE. Bacterial cells treated with P. betle extract demonstrated decreased growth, while the extract was also observed to exhibit inhibition of biofilm formation (70.11%) and demolition of established B. gaemokensis biofilms (57.98%). SEM analysis revealed significant changes to bacterial morphology post treatment with P. betle, with cellular disintegration being prominent. In silico network pharmacology analysis elucidated proteins like ESR1 and IL6 to be majorly involved in biological pathways of dental caries, which also interact with the protective ability of P. betle. Gene Ontology (GO) terms and KEGG pathways were also screened using enrichment analysis. Molecular docking demonstrated the highest binding affinity of Spirost-8-en-11-one,3-hydroxy-,(3ß,5α,14ß,20ß,22ß,25R) with bacterial proteins FabI (-12 kcal/mol), MurB (-17.1 kcal/mol), and FtsZ (-14.9 kcal/mol). Therefore, it is suggested that P. betle can serve a potentially therapeutic role and could be used in the preparation of herbal formulations for managing bacterial flora.

Antibacterial efficacy of silver nanoparticles (AgNPs) against metallo-ß-lactamase and extended spectrum ß-lactamase producing clinically procured isolates of Pseudomonas aeruginosa.

Resistance to carbapenems is a global threat, especially in developing countries with limited health resources. Prevalence, antibiogram, PCR detection of antibiotic resistance genes, and potency of Silver Nanoparticles (AgNPs) against multidrug-resistant (MDR) Pseudomonas aeruginosa were studied. Kirby-Bauer disc method and PCR were used to study antibiogram and drug resistance genes respectively in 255 isolates of Pseudomonas aeruginosa obtained from a tertiary care hospital. Silver nitrate (AgNO3) precursor salts were reacted with Aspergillus flavus culture filtrate to trigger the extracellular mycosynthesis of AgNPs. Mycosynthesis was first monitored regularly by visible ultraviolet spectroscopy that recorded AgNP peaks of approximately 400-470 nm. Confirmation by Transmission electron micrographs provided confirmation of AgNPs formed within a range of 5-30 nm. Individual and combined antibacterial activity of ten antibiotics and AgNPs was analyzed. Pearson correlation coefficients (r) were calculated for phenotypic and genotypic multidrug resistance. Data were evaluated using SPSS version 20. p-value < 0.05 was considered statistically significant. 61.5% were carbapenemase producers (p < 0.01). The recorded frequency of blaIMP-1, blaSHV, blaVIM, blaOXA, and blaTEM were 13%, 32%, 15%, 21%, and 43%, respectively. The reducing order of antimicrobial activity of antibiotics and AgNPs was piperacillin/tazobactam + AgNPs (31 mm), cefoxitin + AgNPs (30 mm) > amikacin + AgNPs (25 mm) > aztreonam + AgNPs (23 mm) > meropenem + AgNPs (22 mm) > imipenem + AgNPs (20 mm) > gentamycin + AgNPs (17 mm) > ciprofloxacin + AgNPs (16 mm) > cefoperazone/sulbactam + AgNPs (14 mm) ≥ ceftazidime + AgNPs (14 mm). The conjugated effect of AgNPs plus antibiotics showed a 0.15-3.51 (average of 2.09) fold-area augmentation of antimicrobial activity. AgNPs conjugated with antibiotics effectively inhibited MDR Pseudomonas aeruginosa. To the best of our understanding, this is an inaugural report from Punjab Pakistan enlisting co-expression of Metallo-ß-lactamases, extended-spectrum ß-lactamases, and AmpC-ß-lactamase plus activity of antibiotic-AgNPs.

Synergistic efficacy of colistin and silver nanoparticles impregnated human amniotic membrane in a burn wound infected rat model.

Antimicrobials used to treat burn wound infections have become multidrug-resistant, thus delaying wound healing. When combined with silver nanoparticles, antibiotics create a multifaceted antibacterial mechanism of action to which bacteria are incapable of developing resistance. Similarly, the amniotic membrane has been found to lower the bacterial number. The purpose of the current study was to observe the antibacterial activity of combined topical colistin with silver nanoparticles and decellularized human amniotic membrane as a dressing in burn wounds infected with bacteria with the goal of promoting faster healing. Bacteria commonly isolated from burn wounds and the most sensitive topical antibiotic were identified. Colistin, silver nanoparticles and combined colistin with silver nanoparticles were impregnated into decellularized human amniotic membranes. These wound dressings were evaluated in third-degree multidrug-resistant bacterial infected thermal burns induced in rats. Out of a total of 708 pus samples from burn wounds, Pseudomonas aeruginosa was the most prevalent pathogen 308 (43.5%), followed by Klebsiella pneumoniae 300 (42.4%). Topical colistin was 100% sensitive for both bacteria. Overall, maximum wound contraction (p < 0.05), and increased collagen deposition (+++) with no isolation of bacteria from wound swabs were noted on day 21 for the combined colistin with silver nanoparticle-loaded human amniotic membrane dressing group. Our study concluded that the increased antimicrobial activity of the novel combination of colistin and silver nanoparticle-loaded decellularized human amniotic membrane manifested its potential as an effective burn wound dressing.

SPECIAL ARTICLE COVID-19: ENT Manifestations in Patients Suffering from COVID- 19: Study from a COVID Hospital in North India

Abstract Introduction COVID-19 has been one of the worst pandemics faced by the human civilization, and otorhinolaryngological manifestations are commonly seen in this disease. Objective The present study was done to profile the ear, nose, and throat (ENT) manifestations in patients diagnosed with COVID-19. An attempt has also been made to assess whether there was any difference between the symptoms of different strains of COVID-19. A brief review of the current knowledge of the transmission of the disease and its treatment has also been done. Methods A cross-sectional, record-based study was conducted in a COVID hospital of India between May and July 2020. Descriptive statistics were used and appropriate parametric/nonparametric tests were applied to assess the association between various variables. Results Out of 250 patients, 80 cases were asymptomatic and 170 were symptomatic. Most of the symptomatic patients had sore throat and nasal congestion. Conclusion Knowledge of the ENT manifestations of COVID-19 is essential for its early identification and to devise appropriate prevention protocols for the benefit of health care workers (HCWs) and of the general population.

Miniaturized thermal acoustic gas sensor based on a CMOS microhotplate and MEMS microphone.

We present a miniaturised thermal acoustic gas sensor, fabricated using a CMOS microhotplate and MEMS microphone. The sensing mechanism is based on the detection of changes in the thermal acoustic conversion efficiency which is dependent on the physical properties of the gas. An active sensing element, consisting of a MEMS microphone, is used to detect the target gas while a reference element is used for acoustic noise compensation. Compared to current photoacoustic gas sensors, our sensor requires neither the use of gas-encapsulated microphones, nor that of optical filters. In addition, it has all the benefits of CMOS technology, including production scalability, low cost and miniaturization. Here we demonstrate its application for CO[Formula: see text] gas detection. The sensor could be used for gas leak detection, for example, in an industrial plant.

ENT Manifestations in Patients Suffering from COVID-19: Study from a COVID Hospital in North India.

Introduction COVID-19 has been one of the worst pandemics faced by the human civilization, and otorhinolaryngological manifestations are commonly seen in this disease. Objective The present study was done to profile the ear, nose, and throat (ENT) manifestations in patients diagnosed with COVID-19. An attempt has also been made to assess whether there was any difference between the symptoms of different strains of COVID-19. A brief review of the current knowledge of the transmission of the disease and its treatment has also been done. Methods A cross-sectional, record-based study was conducted in a COVID hospital of India between May and July 2020. Descriptive statistics were used and appropriate parametric/nonparametric tests were applied to assess the association between various variables. Results Out of 250 patients, 80 cases were asymptomatic and 170 were symptomatic. Most of the symptomatic patients had sore throat and nasal congestion. Conclusion Knowledge of the ENT manifestations of COVID-19 is essential for its early identification and to devise appropriate prevention protocols for the benefit of health care workers (HCWs) and of the general population.

One-step SYBR green-based real-time RT-PCR assay for detection of foot-and-mouth disease virus circulating in India.

Rapid, sensitive, and reliable laboratory detection of foot-and-mouth disease virus (FMDV) infection is essential for containing and controlling virus infection in any geographical area. In this report a SYBR green-based 3Dpol-specific one-step real-time RT-PCR (rRT-PCR) assay was developed for the pan-serotype detection of FMDV in India. The detection limit of the SYBR green-based rRT-PCR was 10-2 TCID50/50 µl, which is 10 times more sensitive than the traditional agarose gel electrophoresis-based RT-multiplex PCR (RT-mPCR). The standard curve exhibited a linear range across 8-log10 units of viral RNA dilution. The reproducibility and specificity of this assay were reasonably high suggesting that the 3Dpol-specific SYBR green rRT-PCR could detect FMDV genome specifically and with little run-to-run variation. The new 3Dpol-specific SYBR green rRT-PCR assay was evaluated alongside the established RT-mPCR using the archived FMDV isolates and clinical field samples from suspected FMD outbreaks. A perfect concordance was observed between the new rRT-PCR and the traditional RT-mPCR on viral RNA in the archived FMDV cell culture isolates tested. Furthermore, 73% of FMDV-suspected clinical samples were detected positive through the 3Dpol-specific SYBR green rRT-PCR, while the detection rate through the traditional RT-mPCR was 57%. Therefore, the SYBR green-based 3Dpol-specific one-step rRT-PCR could be considered as a valuable assay with higher diagnostic sensitivity to complement the routine assays that are being used for FMD virus diagnosis in India.

Experimental evolution reveals sex-specific dominance for surviving bacterial infection in laboratory populations of Drosophila melanogaster.

Males and females are subjected to distinct kinds of selection pressures, often leading to the evolution of sex-specific genetic architecture, an example being sex-specific dominance. Sex-specific dominance reversals (SSDRs), where alleles at sexually antagonistic loci are at least partially dominant in the sex they benefit, have been documented in Atlantic salmon, rainbow trout, and seed beetles. Another interesting feature of many sexually reproducing organisms is the asymmetric inheritance pattern of X chromosomes, which often leads to distinct evolutionary outcomes on X chromosomes compared to autosomes. Examples include the higher efficacy of sexually concordant selection on X chromosomes, and X chromosomes being more conducive to the maintenance of sexually antagonistic polymorphisms under certain conditions. Immunocompetence is a trait that has been extensively investigated for sexual dimorphism with growing evidence for sex-specific or sexually antagonistic variation. X chromosomes have been shown to harbor substantial immunity-related genetic variation in the fruit fly, Drosophila melanogaster. Here, using interpopulation crosses and cytogenetic cloning, we investigated sex-specific dominance and the role of the X chromosome in improved postinfection survivorship of laboratory populations of D. melanogaster selected against pathogenic challenge by Pseudomonas entomophila. We could not detect any contribution of the X chromosome to the evolved immunocompetence of our selected populations, as well as to within-population variation in immunocompetence. However, we found strong evidence of sex-specific dominance related to surviving bacterial infection. Our results indicate that alleles that confer a survival advantage to the selected populations are, on average, partially dominant in females but partially recessive in males. This could also imply an SSDR for overall fitness, given the putative evidence for sexually antagonistic selection affecting immunocompetence in Drosophila melanogaster. We also highlight sex-specific dominance as a potential mechanism of sex differences in immunocompetence, with population-level sex differences primarily driven by sex differences in heterozygotes.

A highly stable, nanotube-enhanced, CMOS-MEMS thermal emitter for mid-IR gas sensing.

The gas sensor market is growing fast, driven by many socioeconomic and industrial factors. Mid-infrared (MIR) gas sensors offer excellent performance for an increasing number of sensing applications in healthcare, smart homes, and the automotive sector. Having access to low-cost, miniaturized, energy efficient light sources is of critical importance for the monolithic integration of MIR sensors. Here, we present an on-chip broadband thermal MIR source fabricated by combining a complementary metal oxide semiconductor (CMOS) micro-hotplate with a dielectric-encapsulated carbon nanotube (CNT) blackbody layer. The micro-hotplate was used during fabrication as a micro-reactor to facilitate high temperature (>700 [Formula: see text]C) growth of the CNT layer and also for post-growth thermal annealing. We demonstrate, for the first time, stable extended operation in air of devices with a dielectric-encapsulated CNT layer at heater temperatures above 600 [Formula: see text]C. The demonstrated devices exhibit almost unitary emissivity across the entire MIR spectrum, offering an ideal solution for low-cost, highly-integrated MIR spectroscopy for the Internet of Things.

Predictors of slow clinical response and extended treatment in patients with extra-pulmonary tuberculosis in Pakistan, A hospital-based prospective study.

The optimal duration of treatment in different forms of extrapulmonary tuberculosis (EPTB) is not clearly defined. This study aimed to identify predictors of slow clinical response and extended anti-TB treatment in EPTB patients. Socio-demographic, clinical, and microbiological characteristics of EPTB patients registered for anti-TB treatment at a tertiary care hospital, were analysed for identification of predictors of extended treatment. A total of 251 patients (137 lymphadenitis, and 114 pleuritis) were included in the analysis. Treatment was extended to more than 6 months in 58/251 (23%) patients. In the multivariate regression analysis, culture-positive EPTB (p = 0.007) [OR (95% CI) = 3.81 (1.43, 10.11)], history of diabetes (p = 0.014) [OR (95% CI) = 25.18 (1.94, 325.83)], smokeless tobacco use (p = 0.002) [OR (95% CI) = 17.69 (2.80, 111.72)], and slow regression of local signs and symptoms after 2 months of treatment (p < 0.001) [OR (95% CI) = 17.09 [(5.79, 50.39)] were seen to be significantly associated with treatment extension. Identification of predictors of extended treatment can help clinical decisions regarding optimal duration of treatment. Further studies are needed to identify subgroups of EPTB patients who can benefit from a shorter or longer treatment regimen.

Antibiogram and molecular characterization of multi-drug resistant microorganisms isolated from urinary tract infections.

Bacteria are the commonest etiological factor among the microbes that cause UTIs. The most prevalent bacteria identified in the lab are Escherichia coli, Klebsiella pneumonia and Pseudomonas aeruginosa. Antibiotics are the empiric therapy for such infections but the reoccurrence rate is becoming high owing to the development of resistance due to their irrational and indiscriminate use across the globe. This study was designed on UTI cases of OPD, Medical, Nephrology, Surgical, Main OT, Urology and ICU wards of Allied hospital Faisalabad. 11 antibiotics were used which showed that E. coli is sensitive to Amikacin, Gentamicin, Imipenem, Piperacillin tazobactam, and Polymyxin B. Klebsiella pneumonia showed sensitivity for Amikacin, Gentamicin, Nitrofurantoin, Imipenem, Polymyxin B, Piperacillin tazobactam and Trimethoprim-sulfamethoxazole. While Pseudomonas aurignosa showed resistance to Amikacin, Ciprofloxacin, Gentamicin, Piperacillin tazobactam, Imipenem, and Polymyxin B. E. coli exhibited the highest sensitivity for Piperacillin tazobactam, Klebsiella pneumonia for Imipenem and Pseudomonas aurignosa for Ciprofloxacin. Further, the isolated DNA samples of these microorganisms were confirmed by gel electrophoresis and subjected to molecular characterization by performing trace file and phylogenetic tree analysis.

Sperm Cyst "Looping": A Developmental Novelty Enabling Extreme Male Ornament Evolution.

Postcopulatory sexual selection is credited as a principal force behind the rapid evolution of reproductive characters, often generating a pattern of correlated evolution between interacting, sex-specific traits. Because the female reproductive tract is the selective environment for sperm, one taxonomically widespread example of this pattern is the co-diversification of sperm length and female sperm-storage organ dimension. In Drosophila, having testes that are longer than the sperm they manufacture was believed to be a universal physiological constraint. Further, the energetic and time costs of developing long testes have been credited with underlying the steep evolutionary allometry of sperm length and constraining sperm length evolution in Drosophila. Here, we report on the discovery of a novel spermatogenic mechanism-sperm cyst looping-that enables males to produce relatively long sperm in short testis. This phenomenon (restricted to members of the saltans and willistoni species groups) begins early during spermatogenesis and is potentially attributable to heterochronic evolution, resulting in growth asynchrony between spermatid tails and the surrounding spermatid and somatic cyst cell membranes. By removing the allometric constraint on sperm length, this evolutionary innovation appears to have enabled males to evolve extremely long sperm for their body mass while evading delays in reproductive maturation time. On the other hand, sperm cyst looping was found to exact a cost by requiring greater total energetic investment in testes and a pronounced reduction in male lifespan. We speculate on the ecological selection pressures underlying the evolutionary origin and maintenance of this unique adaptation.

In vivo prophylactic efficacy of Lactobacillus reuteri MT180537 against aerobic vaginitis.

Aerobic vaginitis is a recently described vaginal infection that is treated with antibiotics, which cause undesirable effects leading to disturbance in normal vaginal flora and antibiotic resistance among pathogens. Probiotics may be considered as a natural alternative therapy. We investigated antagonistic and immunomodulatory potential of intravaginally administered probiotic Lactobacillus reuteri-MT180537 against vaginal colonization by Enterococcus faecalis-MW051601 in mice. In vitro antimicrobial potential of lactic acid bacteria was determined against major pathogens of aerobic vaginitis. Moreover, in vivo prophylactic efficacy of L. reuteri-MT180537 against E. faecalis-MW051601 induced AV, in ß-estradiol immunosuppressed mice was determined for the first time. Lactic acid bacteria displayed antibacterial activity against pathogens with zone of inhibition (11.33-20.00 mm) and co-aggregation (40-67%). Animals receiving L. reuteri-MT180537 followed by E. faecalis-MW051601 challenge exhibited significant reduction in clinical index, vaginal bacterial load, and histopathological changes in vaginal tissues compared to animals receiving E. faecalis-MW051601 only. L. reuteri-MT180537 upregulated expression of anti-inflammatory (Foxp3, IFN-γ) cytokines and resulted in controlling E. faecalis-MW051601 induced over expression of pro-inflammatory (IL-6, IL-1ß) cytokines. Altogether, L. reuteri-MT180537 displayed antagonistic properties in vitro and prevented aerobic vaginitis by inhibiting the growth of E. faecalis-MW051601 and regulating expression of pro-inflammatory and anti-inflammatory cytokines in mice.

Host biomarkers for monitoring therapeutic response in extrapulmonary tuberculosis.

PURPOSE: The aim of this study was to explore the utility of inflammatory biomarkers in the peripheral blood to predict response to treatment in extrapulmonary tuberculosis (EPTB). METHODS: A Luminex xMAP-based multiplex immunoassay was used to measure 40 inflammatory biomarkers in un-stimulated plasma of 91 EPTB patients (48 lymphadenitis, and 43 pleuritis) before and at 2 and 6 months of treatment. RESULTS: Overall a significant change was observed in 28 inflammatory biomarkers with treatment in EPTB patients. However, MIG/CXCL9, IP-10/CXCL10, and CCL23 decreased in all patients' groups with successful treatment at both time points. At 2 months, 29/64 (45%) patients responded partially while 35/64 (55%) showed complete regress. Among good responders, a higher number of biomarkers (16/40) reduced significantly as compared to partial responders (1/40). Almost half (14/29) of partial responders required longer treatment than 6 months to achieve satisfactory response. The levels of MIG, IP-10, MIF, CCL22 and CCL23 reduced significantly among 80, 74, 60, 71, 51% good responders, as compared to 52, 52, 52, 59, 52% partial responders, respectively. A biosignature, defined by a significant decrease in any one of these five biomarkers, corresponded with satisfactory response to treatment in 97% patients at 2 month and 99% patients at 6 months of treatment. CONCLUSION: Change in inflammatory biomarkers correlates with treatment success. A five biomarker biosignature (MIG, IP-10, MIF, CCL22 and CCL23) could be used as an indicator of treatment success.