Secondary Intention Healing After Debridement for Bilateral Periorbital Necrotizing Fasciitis.

A 75-year-old male with a history of poorly controlled diabetes, hypertension, coronary artery disease, chronic obstructive pulmonary disease, and obesity presented with severe bilateral periorbital edema with necrosis and purulent discharge. Although hemodynamically stable, laboratory markers indicated systemic toxicity. Imaging showed bilateral periorbital edema extending into the frontal scalp, temporal fossa, and right orbit. Suspected to have necrotizing fasciitis, the patient underwent urgent debridement of bilateral upper and lower eyelids and was found to have postseptal extension of necrosis into the right orbit. During his hospitalization, he was treated with broad-spectrum antimicrobials and underwent a second surgery for exploration and debridement. The patient was lost to follow-up and found to have healed by secondary intention without any surgical reconstruction. Our case demonstrates not only a rare case of necrotizing fasciitis involving all 4 eyelids, but also an exceptional cosmetic and functional result after secondary intention healing.

Fatal Oedipism: A Case Report and Literature Review.

PURPOSE: To describe a unique case of a fatal self-enucleation and review previously published cases. METHODS: The authors describe a unique case of a complete unilateral self-enucleation while under the influence of drugs, which resulted in severe intracranial hemorrhages, right internal carotid artery opacification, and death. A literature review was performed by searching articles published before January 2023 in the Pubmed/MEDLINE database using the keywords "auto-enucleation or self-enucleation." Cases of self-inflicted damage to the globe without severing any connections were excluded. RESULTS: A literature review identified a total of 54 articles and 75 patients who had self-enucleated at least one globe completely (84.0%). Their average age was 37 years and 50.7% were male. At the time of auto-enucleation, 64.0% of these patients had known psychiatric disorders, and 28.0% were found to be under the influence of illicit drugs or alcohol. Auto-enucleation resulted in intracranial complications in 26.7% of cases. There has been 1 prior case, which, like the authors' case, resulted in death due to intracranial complications. However, this occurred in a patient who partially enucleated one eye after a self-inflicted injury to the fellow eye. The current case is unique as these complications resulted from a complete unilateral auto-enucleation. CONCLUSIONS: The severity of this case's presentation and outcome highlights the importance of prompt neuroimaging and a thorough assessment. Prompt psychiatric assessment and treatment are also required.

Diffusion-Weighted Imaging of the Orbit: A Case Series and Systematic Review.

PURPOSE: To describe the findings of diffusion-weighted imaging (DWI) for a series of orbital lesions and provide a systematic review of relevant literature. METHODS: A retrospective review of 20 patients with orbital lesions who underwent MRI with DWI at two academic institutions between 2015 and 2020 was performed. Lesion diagnosis was histopathologically confirmed except a presumed cavernous hemangioma. Echoplanar diffusion-weighted images had been acquired using 2 or 3 b values (b=0 and 1000 or b=0, 500, and 1000) at 1.5T or 3T. Lesions with significant artifacts were excluded. DWI sequences were analyzed by neuro-radiologists blinded to the diagnosis. Mean ADC values of lesions were calculated from a single region of interest. An independent two-tailed t test was used to compare categories of lesions with p < 0.05 considered significant. A systematic review of the literature was performed. RESULTS: Our study included 21 lesions. ADC values were significantly lower for malignant lesions (0.628 ± 0.125 × 10 -3 mm 2 /s) than inflammatory lesions (1.167 ± 0.381 × 10 -3 mm 2 /s) ( p < 0.001). ADC values were significantly lower for orbital lymphoma (mean 0.621 ± 0.147 × 10 -3 mm 2 /s) than idiopathic orbital inflammation (mean 1.188 ± 0.269 × 10 -3 mm 2 /s) with no overlap ( p < 0.001). CONCLUSIONS: Orbital malignancies demonstrated lower ADC values, while inflammatory processes demonstrated higher ADC values, except IgG4-related disease. DWI and ADC values differentiated idiopathic orbital inflammation from orbital lymphoma. This study highlights the role of DWI in evaluating orbital pathology.

A comparison of primary and secondary eye removal after open globe injury: A multi-centre study.

BACKGROUND/OBJECTIVES: Our goal was to compare the characteristics and surgical outcomes of patients who underwent primary eye removal surgery after open globe injury with those who underwent secondary eye removal surgery after open globe repair. SUBJECTS/METHODS: This was a retrospective review of subjects who underwent evisceration or enucleation within 3 months of an open globe injury, at three Level I trauma centres in three U.S. cities between July 2014 and July 2020. RESULTS: 19 patients underwent primary eye removal and 20 underwent secondary eye removal. The most common mechanism of trauma in patients who underwent primary eye removal was gunshot. Compared to the secondary eye removal group, patients who underwent primary eye removal were significantly more likely to be male; have longer hospital stays; be discharged to another care facility rather than home; have facial fractures; suffer intracranial injury; and be unable to consent themselves for surgery. Both groups had a low surgical complication rate with one case of socket contracture in each group. CONCLUSIONS: The standard of care for an open globe injury is prompt repair, but there are occasions when the globe is so damaged that it is deemed unrepairable. We found that globes that required primary eye removal were more often due to gunshot wounds, and that there was greater morbidity associated with these injuries. The authors' preferred surgical approach was evisceration with placement of a silicone sphere; patient outcomes demonstrate that this method was found to be safe, with a low complication and infection rate.

Pediatric cavernous sinus and superior ophthalmic vein thrombophlebitis complicated by peri-venous orbital abscesses.

Purpose: This case report documents a 13-year-old male with bilateral cavernous sinus thrombosis and left superior ophthalmic vein thrombosis secondary to sphenoid sinusitis who subsequently developed peri-venous orbital abscesses. Observations: Although the patient initially improved clinically with intravenous antibiotic therapy and therapeutic anticoagulation, his symptoms returned and repeat imaging demonstrated two well-circumscribed, rim-enhancing lesions in the left orbit concerning for abscesses. Surgical intervention revealed that these purulent collections were contiguous with the superior and inferior ophthalmic veins with the superior collection also containing hemorrhagic material. Despite aggressive management, the abscess in the inferolateral orbit recurred, requiring repeat surgical intervention. The patient was ultimately discharged on parenteral antibiotics and anticoagulation, and on outpatient follow-up, there was no evidence of recurrence. Conclusions and Importance: This case report describes a pediatric patient with bilateral cavernous sinus thrombosis who developed the rare complication of multiple peri-venous orbital abscesses despite appropriate treatment with antibiotics. The patient's complex clinical course highlights the importance of prompt repeat imaging and possible surgical intervention upon clinical changes, especially in patients with infections from the Streptococcus milleri group.

Lactate-Dependent Cross-Talk Between Astrocyte and GnRH-I Neurons in Hypothalamus of Aged Brain: Decreased GnRH-I Transcription.

GnRH-I produced by hypothalamic neurosecretory cells is considered a master regulator of mammalian reproduction. Although GnRH-I transcription is well studied, the effect of ageing on transcriptional regulation of GnRH-I has not yet been explored. Here, we elucidate the effects of ageing on the metabolic environment like lactate level and TNF-α and how these affect GnRH-I transcription. Using pathway analysis of transcriptomic data, we found that lactate is upregulated in ageing astrocytes due to the downregulation of cellular respiration pathways possibly resulting in greater pyruvate concentration for lactate production. This lactate could then be shuttled into neurons where it would affect GnRH-I transcription. We showed that supra-physiological level of lactate in young mouse brain can mimic metabolic disturbances in the old brain and cause downregulation in GnRH-I transcription at a young age. In particular, we found upregulation of GnRH-I repressors in the young brain treated with high levels of lactate similar to old brain. Hence, this confirmed that aged metabolic environment can affect GnRH-I transcription even in the young brain. Further downstream analysis using the TRUST database showed NF-Kb signalling which lies downstream of both lactate and TNF-α as being capable of upregulating GnRH-I repressors. Since NF-Kb signalling has been shown in our study as well as others to be induced by TNF-α during ageing, it is likely that GnRH-I transcriptional regulation is mediated through these pathways. Thus, we formed a model for explaining the downregulation of GnRH-I transcription during ageing through differential expression of its TFs in an aged metabolic environment.

Bilateral periorbital leukemia cutis presenting as suspected cellulitis.

Many conditions present with periorbital edema and erythema, mimicking preseptal cellulitis. We report the unique case of a patient with relapsed monoblastic mutant isocitrate dehydrogenase-2 (IDH2) acute myeloid leukemia (AML) who presented with periorbital edema and erythema, unresponsive to antibiotics. Histopathology from punch biopsy was consistent with leukemia cutis. The patient responded rapidly to the initiation of enasidenib, a novel targeted inhibitor of mutant IDH2 enzymes. Our case highlights the importance of considering leukemia cutis in patients with a history of leukemia presenting with periorbital edema and erythema.

Delineating the Role of Aedes aegypti ABC Transporter Gene Family during Mosquito Development and Arboviral Infection via Transcriptome Analyses.

Aedes aegypti acts as a vector for several arboviral diseases that impose a major socio-economic burden. Moreover, the absence of a vaccine against these diseases and drug resistance in mosquitoes necessitates the development of new control strategies for vector-borne diseases. ABC transporters that play a vital role in immunity and other cellular processes in different organisms may act as non-canonical immune molecules against arboviruses, however, their role in mosquito immunity remains unexplored. This study comprehensively analyzed various genetic features of putative ABC transporters and classified them into A-H subfamilies based on their evolutionary relationships. Existing RNA-sequencing data analysis indicated higher expression of cytosolic ABC transporter genes (E & F Subfamily) throughout the mosquito development, while members of other subfamilies exhibited tissue and time-specific expression. Furthermore, comparative gene expression analysis from the microarray dataset of mosquito infected with dengue, yellow fever and West Nile viruses revealed 31 commonly expressed ABC transporters suggesting a potentially conserved transcriptomic signature of arboviral infection. Among these, only a few transporters of ABCA, ABCC and ABCF subfamily were upregulated, while most were downregulated. This indicates the possible involvement of ABC transporters in mosquito immunity.

Ischemic Proliferative Retinopathy as the Presenting Feature of Systemic Sarcoidosis.

Purpose: This work reports a case of systemic sarcoidosis presenting with ischemic ocular manifestations without uveitis. Methods: This case report describes a 28-year-old White male who presented with pain, redness, and blurry vision of his left eye for 1 month who was found to have proliferative retinopathy and neovascular glaucoma. Results: Normal fasting blood glucose and glycated hemoglobin A1c levels warranted further investigation. Abnormal findings from chest x-ray of hilar lymphadenopathy as well as an elevated angiotensin-converting enzyme level were suggestive of sarcoidosis, and they were further confirmed by histopathology derived through bronchoscopy. Conclusions: Systemic sarcoidosis may present with rapidly progressing ischemic retinopathy without signs of inflammation, which may obscure the diagnosis. Such presentation may be misdiagnosed, which may result in delayed treatment and poor outcome.

Heme-Peroxidase 2, a Peroxinectin-Like Gene, Regulates Bacterial Homeostasis in Anopheles stephensi Midgut.

The dynamic nature of mosquito gut microbiome is associated with different stages of development and feeding behaviors. Therefore, mosquito gut harbors a wide range of endogenous microbes that promote numerous life processes such as, nutrition, reproduction and immunity. In addition, gut microbiota also play an important role in the regulation of Plasmodium (malaria parasite) development. Thus, understanding the mechanism of microbial homeostasis in mosquito gut might be one of the strategies to manipulate malaria parasite development. In the present study, we characterized a 692 amino acids long secreted midgut heme-peroxidase 2 (AsHPX2) in Anopheles stephensi, the major Indian malaria vector. The presence of putative integrin binding motifs, LDV (Leu-Asp-Val), indicated its peroxinectin-like nature. Our phylogenetic analysis revealed that AsHPX2 is a Culicinae lineage-specific gene. RNA interference (RNAi)-mediated silencing of AsHPX2 gene significantly enhanced the growth of midgut bacteria in sugar-fed mosquitoes against sham-treated controls. Interestingly, blood-feeding drastically reduced AsHPX2 gene expression and enhanced the growth of midgut bacteria. These results revealed a negative correlation between the expression of AsHPX2 gene and gut bacterial growth. We proposed that AsHPX2, being a mosquito-specific gene, might serve as a "potent target" to manipulate midgut microbiota and vector competence.

Immediate Release of Vitreomacular Traction After Pneumatic Vitreolysis Followed by the Drinking Bird Technique.

Purpose: To report a case of release of vitreomacular traction (VMT) in a patient with a full thickness macular hole (FTMH) immediately following pneumatic vitreolysis (PV) combined with head bobbing movements. Methods: A 71-year-old female with VMT and an FTMH presented with blurred vision for 2 months to the level of 20/400. At her 1-month follow-up visit, PV was performed using C3F8 gas and she was instructed to perform the drinking bird technique for ten minutes. Results: Optical coherence tomography performed ten minutes after PV with head bobbing showed VMT release and a smaller FTMH. Visual acuity improved to 20/150 immediately afterwards and to 20/80 two months later. Conclusions: Using the drinking bird technique for a continuous period of time immediately following PV may encourage rapid VMT release. PV may be a feasible option for patients with VMT and FTMH who do not want surgery.

Reproducibility of minimum rim width and retinal nerve fibre layer thickness using the Anatomic Positioning System in glaucoma patients.

OBJECTIVE: To determine the test-retest repeatability of minimum rim width and retinal nerve fibre layer thickness measurements obtained by spectral-domain optical coherence tomography using the Anatomic Positioning System protocol in glaucoma patients and controls. Also, to assess the ability of the minimum rim width and retinal nerve fibre layer thickness to diagnose glaucoma in 2 circular peripapillary locations. METHODS: Spectral domain optical coherence tomography scans of the optic nerve head were obtained twice during the same visit using the Anatomic Positioning System eye-tracking protocol. The minimum rim width and retinal nerve fibre layer thickness were measured at 3 circular diameters (3.5 mm, 4.1 mm, and 4.7 mm). Intraclass correlation coefficients and area under the receiver operating characteristic were calculated for these parameters. RESULTS: A total of 36 glaucomatous eyes and 59 control eyes were included in the analysis. The intraclass correlation coefficients of minimum rim width and retinal nerve fibre layer thickness global measurement for 3.5 mm and 4.1 mm circles ranged between 0.98 and 1.00 and for 4.7 mm circle was between 0.76 and 1.00. The minimum rim width had an area under the receiver operating characteristic of 0.97, while the retinal nerve fibre layer thickness measurements had an area under the receiver operating characteristic of 0.95, 0.95, and 0.96 for the 3.5 mm, 4.1 mm, and 4.7 mm circles, respectively. CONCLUSIONS: The minimum rim width and retinal nerve fibre layer thickness measurements using the Anatomic Positioning System protocol had overall excellent reproducibility and diagnostic performance. Using this protocol and the novel minimum rim width parameter may be useful in more accurate diagnosis and follow-up of patients with glaucoma.

Anopheles stephensi Dual Oxidase Silencing Activates the Thioester-Containing Protein 1 Pathway to Suppress Plasmodium Development.

We characterized the dual oxidase (Duox) gene in the major Indian malaria vector Anopheles stephensi, which regulates the generation of reactive oxygen species. The AsDuox gene encodes for a 1,475-amino-acid transmembrane protein that contains an N-terminal noncytoplasmic heme peroxidase domain, a calcium-binding domain, seven transmembrane domains, and a C-terminal cytoplasmic NADPH domain. Phylogenetic analyses revealed that A. stephensi Duox protein is highly conserved and shares 97-100% amino acid identity with other anopheline Duoxes. AsDuox is expressed in all the developmental stages of A. stephensi and the pupal stages revealed relatively higher expressions. The Duox gene is induced in Plasmodium-infected mosquito midguts, and RNA interference-mediated silencing of this gene suppressed parasite development through activation of the thioester-containing protein 1 pathway. We propose that this highly conserved anopheline Duox, being a Plasmodium agonist, is an excellent target to control malaria parasite development inside the insect host.

Identification, characterization and expression analysis of Anopheles stephensi double peroxidase.

Peroxidases catalyze the reduction of peroxides and that, in turn, oxidize various substrates. They have been widely reported to play an important role in mosquito innate immunity against various pathogens. Here, we have characterized double heme peroxidase (AsDBLOX) gene from the Indian malaria vector Anopheles stephensi. It is a true ortholog of An. gambiae DBLOX. This 4209 bp AsDBLOX gene encodes for a protein of 1402 amino acids that has two duplicated peroxidase domains, domain I (from amino acid 61 to 527) and domain II (from amino acid 714 to 1252). The first domain has only substrate binding sites and lacks all other motifs of a functional heme peroxidase (e.g. heme binding site, calcium binding site and homodimer interface). Instead, it has two integrin binding motifs-LDV (Leu-Asp-Val) and RGD (Arg-Gly-Asp). The second peroxidase domain, however, has all the features of a complete heme peroxidase along with an integrin binding motif LDI (Leu-Asp-Ile). Thus, AsDBLOX gene is a unique type of peroxinectin as these groups of proteins are characterized by integrin binding motifs along with a heme peroxidase domain. We also observed that the AsDBLOX gene is expressed in all the life cycle stages of mosquito and is highly induced in the pupal stage of development which indicates its possible role in development.

Establishment of a normative database and evaluation of the test-retest repeatability of the Spaeth/Richman contrast sensitivity test.

PURPOSE: To evaluate the test-retest repeatability of a computer-based contrast sensitivity (CS) test, the Spaeth/Richman contrast sensitivity (SPARCS) test, and to determine the effects of age and lens status on CS in normal eyes. STUDY DESIGN: Prospective cross-sectional study. METHODS: The participants were assessed by use of the SPARCS test in each eye 3 times. The first 2 sessions were supervised, while the third was unsupervised. CS was determined for 5 areas of vision (central, superotemporal, superonasal, inferotemporal, and inferonasal) and combined to provide a total score. The test-retest repeatability was determined using Bland-Altman analysis and the intraclass correlation coefficient (ICC). RESULTS: The total SPARCS scores (maximum possible score = 100) ranged from 86.37 (±1.09) (for those aged 20 to 29 years) to 70.71 (±2.64) (for those aged 80 to 87 years). Individuals aged between 10 and 87 years with a normal eye examination (n = 205) were enrolled. When the SPARCS scores for the first 2 sessions were compared, the ICC was 0.79, and the repeated tests were fairly equivalent (mean difference = -0.29, P = .491). The test-retest 95% limits of agreement (95% LoA) ranged from -11.07 to +11.35. When the supervised sessions were compared with the unsupervised session, the ICC was 0.80, and there was slight improvement in the CS scores during the unsupervised session (mean difference = -1.15, P = .0001). The test-retest 95% LoA ranged from -9.18 to +10.60. The CS declined with advanced age and increased cataract severity (P <0.0001). CONCLUSION: Strong agreement was found between repeated SPARCS scores. Older age and increased lens opacity were associated with decline in CS in 5 areas of the visual field. The SPARCS test provides reliable and reproducible assessment of CS in normal eyes.

Apolipophorin-III Acts as a Positive Regulator of Plasmodium Development in Anopheles stephensi.

Apolipophorin III (ApoLp-III) is a well-known hemolymph protein having a functional role in lipid transport and immune responses of insects. Here we report the molecular and functional characterization of Anopheles stephensi Apolipophorin-III (AsApoLp-III) gene. This gene consists of 679 nucleotides arranged into two exons of 45 and 540 bp that give an ORF encoding 194 amino acid residues. Excluding a putative signal peptide of the first 19 amino acid residues, the 175-residues in mature AsApoLp-III protein has a calculated molecular mass of 22 kDa. Phylogenetic analysis revealed the divergence of mosquitoes (Order Diptera) ApoLp-III from their counterparts in moths (Order: Lepidoptera). Also, it revealed a close relatedness of AsApoLp-III to ApoLp-III of An. gambiae. AsApoLp-III mRNA expression is strongly induced in Plasmodium berghei infected mosquito midguts suggesting its crucial role in parasite development. AsApoLp-III silencing decreased P. berghei oocysts numbers by 7.7 fold against controls. These effects might be due to the interruption of AsApoLp-III mediated lipid delivery to the developing oocysts. In addition, nitric oxide synthase (NOS), an antiplasmodial gene, is also highly induced in AsApoLp-III silenced midguts suggesting that this gene acts like an agonist and protects Plasmodium against the mosquito immunity.

Anopheles stephensi Heme Peroxidase HPX15 Suppresses Midgut Immunity to Support Plasmodium Development.

The heme peroxidase HPX15 is an evolutionary conserved anopheline lineage-specific gene. Previously, we found that this gene is present in the genome of 19 worldwide distributed different species of Anopheles mosquito and its orthologs are absent in other mosquitoes, insects, or human. In addition, 65-99% amino acid identity among these 19 orthologs permitted us to hypothesize that the functional aspects of this gene might be also conserved in different anophelines. In this study, we found that Anopheles stephensi AsHPX15 gene is mainly expressed in the midgut and highly induced after uninfected or Plasmodium berghei-infected blood feeding. RNA interference-mediated silencing of midgut AsHPX15 gene drastically reduced the number of developing P. berghei oocysts. An antiplasmodial gene nitric oxide synthase was induced 13-fold in silenced midguts when compared to the unsilenced controls. Interestingly, the induction of antiplasmodial immunity in AsHPX15-silenced midguts is in absolute agreement with Anopheles gambiae. In A. gambiae, AgHPX15 catalyzes the formation of a dityrosine network at luminal side of the midgut that suppresses the activation of mosquito immunity against the bolus bacteria. Thus, a low-immunity zone created by this mechanism indirectly supports Plasmodium development inside the midgut lumen. These indistinguishable functional behaviors and conserved homology indicates that HPX15 might be a potent target to manipulate the antiplasmodial immunity of the anopheline midgut, and it will open new frontiers in the field of malaria control.

The evolutionary divergence of STAT transcription factor in different Anopheles species.

Anopheles mosquito transmits Plasmodium, the malaria causing parasite. Different species of Anopheles mosquito dominate in a particular geographical location and are capable of transmitting specific strains of Plasmodium. It is important to understand the biology of different anophelines to control the parasite transmission. STAT is an evolutionary conserved transcription factor that regulates the parasite development in African malaria vector Anopheles gambiae. Unlike Drosophila and Aedes aegypti, where a single STAT gene plays an important role in immunity, An. gambiae contains one evolutionary conserved STAT-A and another retro-duplicated, introns-less STAT-B gene. To find out whether other species of Anopheles also have two STATs, the available genomic data of different anophelines were used to annotate their STATs through in silico analyses. Our results revealed that Indian malaria vector An. stephensi genome contains two STATs, AsSTAT-A and AsSTAT-B genes. These genes were cloned and confirmed by sequencing. Both AsSTATs were found to be expressed in different development stages of mosquito. However, the relative mRNA levels of evolutionary conserved AsSTAT-A gene were always higher than the retroduplicated AsSTAT-B gene. STAT pathway was activated upon Plasmodium berghei infection, indicated its role in immunity. Furthermore, comparative in silico analysis of eighteen Anopheles species revealed that five species: An. sinensis, An. albimanus, An. darlingi, An. dirus andAn. farauti do not contain STAT-B gene in their genome. Interestingly, thirteen species of the subgenus Anopheles and Cellia that contain both STATs were also mutually diverged. This consequence leads to sequence variability in some significant protein motifs within the STAT-B genes. Phylogenetic analyses indicated that an independent, lineage-specific duplication occurred in the subgenus Cellia after the diversification of series Neomyzomyia from its last common ancestor. In An. atroparvus (subgenus Anopheles), STAT gene underwent recent lineage-specific duplication and give rise to a highly similar STAT-B gene. This suggested that the genetic divergence in various Anopheles species might appeared due to their adaptations to the altered environmental conditions or pathogen encounters.

Silencing of Anopheles stephensi Heme Peroxidase HPX15 Activates Diverse Immune Pathways to Regulate the Growth of Midgut Bacteria.

Anopheles mosquito midgut harbors a diverse group of endogenous bacteria that grow extensively after the blood feeding and help in food digestion and nutrition in many ways. Although, the growth of endogenous bacteria is regulated by various factors, however, the robust antibacterial immune reactions are generally suppressed in this body compartment by a heme peroxidase HPX15 crosslinked mucins barrier. This barrier is formed on the luminal side of the midgut and blocks the direct interactions and recognition of bacteria or their elicitors by the immune reactive midgut epithelium. We hypothesized that in the absence of HPX15, an increased load of exogenous bacteria will enormously induce the mosquito midgut immunity and this situation in turn, can easily regulate mosquito-pathogen interactions. In this study, we found that the blood feeding induced AsHPX15 gene in Anopheles stephensi midgut and promoted the growth of endogenous as well as exogenous fed bacteria. In addition, the mosquito midgut also efficiently regulated the number of these bacteria through the induction of classical Toll and Imd immune pathways. In case of AsHPX15 silenced midguts, the growth of midgut bacteria was largely reduced through the induction of nitric oxide synthase (NOS) gene, a downstream effector molecule of the JAK/STAT pathway. Interestingly, no significant induction of the classical immune pathways was observed in these midguts. Importantly, the NOS is a well known negative regulator of Plasmodium development, thus, we proposed that the induction of diverged immune pathways in the absence of HPX15 mediated midgut barrier might be one of the strategies to manipulate the vectorial capacity of Anopheles mosquito.