ING4 and ING5 are essential for histone H3 lysine 14 acetylation and epicardial cell lineage development.

Inhibitor of growth 4 and 5 (ING4, ING5) are structurally similar chromatin-binding proteins in the KAT6A, KAT6B and KAT7 histone acetyltransferase protein complexes. Heterozygous mutations in the KAT6A or KAT6B gene cause human disorders with cardiac defects, but the contribution of their chromatin-adaptor proteins to development is unknown. We found that Ing5-/- mice had isolated cardiac ventricular septal defects. Ing4-/-Ing5-/- embryos failed to undergo chorioallantoic fusion and arrested in development at embryonic day 8.5, displaying loss of histone H3 lysine 14 acetylation, reduction in H3 lysine 23 acetylation levels and reduced developmental gene expression. Embryonic day 12.5 Ing4+/-Ing5-/- hearts showed a paucity of epicardial cells and epicardium-derived cells, failure of myocardium compaction, and coronary vasculature defects, accompanied by reduced expression of epicardium genes. Cell adhesion gene expression and proepicardium outgrowth were defective in the ING4- and ING5-deficient state. Our findings suggest that ING4 and ING5 are essential for heart development and promote epicardium and epicardium-derived cell fates and imply mutation of the human ING5 gene as a possible cause of isolated ventricular septal defects.

Iron homeostasis governs erythroid phenotype in polycythemia vera.

Polycythemia vera (PV) is a myeloproliferative neoplasm driven by activating mutations in JAK2 that result in unrestrained erythrocyte production, increasing patients' hematocrit and hemoglobin concentrations, placing them at risk of life-threatening thrombotic events. Our genome-wide association study of 440 PV cases and 403 351 controls using UK Biobank data showed that single nucleotide polymorphisms in HFE known to cause hemochromatosis are highly associated with PV diagnosis, linking iron regulation to PV. Analysis of the FinnGen dataset independently confirmed overrepresentation of homozygous HFE variants in patients with PV. HFE influences the expression of hepcidin, the master regulator of systemic iron homeostasis. Through genetic dissection of mouse models of PV, we show that the PV erythroid phenotype is directly linked to hepcidin expression: endogenous hepcidin upregulation alleviates erythroid disease whereas hepcidin ablation worsens it. Furthermore, we demonstrate that in PV, hepcidin is not regulated by expanded erythropoiesis but is likely governed by inflammatory cytokines signaling via GP130-coupled receptors. These findings have important implications for understanding the pathophysiology of PV and offer new therapeutic strategies for this disease.

The 2017 Women's Health Initiative study and use of hormone therapy: an emulated repeated cross-sectional study.

BACKGROUND: Hormone therapy (HT) use among menopausal women declined after negative information from the 2002 Women's Health Initiative (WHI) HT study. The 2017 post-intervention follow-up WHI study revealed that HT did not increase long-term mortality. However, studies on the effects of the updated WHI findings are lacking. Thus, we assessed the impact of the 2017 WHI findings on HT use in Taiwan. METHODS: We identified 1,869,050 women aged 50-60 years, between June and December 2017, from health insurance claims data to compare HT use in the 3 months preceding and following September 2017. To address the limitations associated with interval-censored data, we employed an emulated repeated cross-sectional design. Using logistic regression analysis, we evaluated the impact of the 2017 WHI study on menopausal symptom-related outpatient visits and HT use. In a scenario analysis, we examined the impact of the 2002 trial on HT use to validate our study design. RESULTS: Study participants' baseline characteristics before and after the 2017 WHI study were not significantly different. Logistic regressions demonstrated that the 2017 study had no significant effect on outpatient visits for menopause-related symptoms or HT use among women with outpatient visits. The scenario analysis confirmed the negative impact of the 2002 WHI trial on HT use. CONCLUSIONS: The 2017 WHI study did not demonstrate any impact on either menopause-related outpatient visits or HT use among middle-aged women in Taiwan. Our emulated cross-sectional study design may be employed in similar population-based policy intervention studies using interval-censored data.

The Combined Bra-Line Back-Lift Latissimus Flap (BLBL-LAT Flap) for Aesthetic Breast Reconstruction and Simultaneous Back Contouring.

BACKGROUND: The latissimus dorsi pedicled ('LAT') flap has been a workhorse flap for breast reconstruction for many decades. The asymmetric back scar has been a major source of complaint. In patients with excess back adiposity, we can utilize the skin paddle harvest to improve back contour. We combined the principles of the esthetic bra-line back-lift with the LAT flap to provide simultaneous improvement of both posterior upper trunk adiposity and skin excess, which together form 'back rolls', using a concealed scar. OBJECTIVES: To establish a new surgical technique of combined bra-line back lift with latissimus dorsi flap ('BLBL-LAT flap') for esthetic breast reconstruction. METHODS: This was an IRB-approved retrospective single-surgeon study performed in a national cancer center. We included patients undergoing breast reconstruction using combined BLBL-LAT flap between 2015 and 2023, with a minimum of 6 months follow up. RESULTS: 106 female patients underwent 110 breast reconstructions using BLBL-LAT flap. 75% of patients had prosthesis placement and 25% of patients were 100% autologous. Complication rates were low: 4/106 patients (3.8%) had seroma, needing surgery. Of the 78 reconstructions with implants, 3 (3.8%) had periprosthetic implant infection. One (<1%) patient had partial flap loss and no patients had complete flap loss. Four patients had bilateral BLBL-LAT flap reconstruction. Two unilateral breast reconstruction patients came back for successful symmetrizing bra-line back-lift (without LAT flap breast reconstruction). CONCLUSIONS: The BLBL-LAT flap allows breast reconstruction and simultaneous improvement in back contour, using a scar that can be concealed in a bra. This two-for-one procedure is of particular benefit for patients with high BMI who often have unwanted excess adiposity and laxity of the back. Since this patient population are high risk for free tissue transfer, we propose that the BLBL-LAT flap should be considered the first-line method of autologous breast reconstruction in higher BMI patients.

Molecular profiling reveals features of clinical immunity and immunosuppression in asymptomatic P. falciparum malaria.

Clinical immunity to P. falciparum malaria is non-sterilizing, with adults often experiencing asymptomatic infection. Historically, asymptomatic malaria has been viewed as beneficial and required to help maintain clinical immunity. Emerging views suggest that these infections are detrimental and constitute a parasite reservoir that perpetuates transmission. To define the impact of asymptomatic malaria, we pursued a systems approach integrating antibody responses, mass cytometry, and transcriptional profiling of individuals experiencing symptomatic and asymptomatic P. falciparum infection. Defined populations of classical and atypical memory B cells and a TH2 cell bias were associated with reduced risk of clinical malaria. Despite these protective responses, asymptomatic malaria featured an immunosuppressive transcriptional signature with upregulation of pathways involved in the inhibition of T-cell function, and CTLA-4 as a predicted regulator in these processes. As proof of concept, we demonstrated a role for CTLA-4 in the development of asymptomatic parasitemia in infection models. The results suggest that asymptomatic malaria is not innocuous and might not support the induction of immune processes to fully control parasitemia or efficiently respond to malaria vaccines.

Effects of cultivar, water condition and their interactions on Cd accumulation in rice grains.

Using low Cd accumulation cultivars and managing field water regimes are effective measures to mitigate Cd accumulations in rice grains. However, the effect of the cultivar-water condition interaction (CWI) on grain Cd accumulations has largely been ignored. To solve this problem, pot and hydroponic experiments were conducted using 14 rice cultivars and two contrasting water conditions. The results showed that CWI significantly affected Cd concentrations in rice grains and roots, explaining 8.8% and 22.8% of the total variance, respectively. These CWI effects were derived from cultivar-dependent variations in rhizosphere soil properties [Eh, pH and available Cd associated with root radial oxygen loss (ROL)] and root Cd uptake. In this context, cultivar HH61 exhibited low, stable Cd accumulations, owing to its stably lower translocation rate, root Cd uptake ability and available Cd in its rhizosphere than the other cultivars, which was induced by its lower ROL. Root-to-grain Cd translocation rates were vital in determining Cd accumulations in grain of different cultivars but were independent from CWI. These results indicated that CWI could play an important role in Cd accumulation in rice while stable low-Cd cultivar should possess low ROL under flooding and low root-to-grain Cd translocation rate. The results will provide novel theoretical basis for cultivar selection and hence benefit the extensive use of low-accumulation cultivars and public health.

Predictors of rapidly progressive interstitial lung disease and mortality in patients with autoantibodies against melanoma differentiation-associated protein 5 dermatomyositis.

OBJECTIVE: Anti-melanoma differentiation-associated protein 5 (MDA5)-positive DM is associated with rapidly progressive interstitial lung disease (RP-ILD) and high mortality. This multicentre retrospective study aimed to identify predictors of mortality and RP-ILD. METHODS: Anti-MDA5-positive DM patients were identified from the Hong Kong Myositis Registry and the Clinical Data Analysis and Reporting System. Clinical characteristics were reviewed. Risk factors for mortality and RP-ILD were identified. RESULTS: Among the 116 recruited patients, 100 (86.2%) had ILD, 47 (40.5%) had RP-ILD and 44 (37.9%) patients died. Cox regression analysis revealed RP-ILD [hazard ratio (HR) 9.735 (95% CI 3.905, 24.272)], age >52 years [HR 4.750 (95% CI 1.692, 13.333)], ferritin level >2800 pmol/l [HR 3.042 (95% CI 1.323, 6.997)] and lactate dehydrogenase (LDH) >400 IU/l [HR 2.290 (95% CI 1.009, 5.198)] were independent predictors of mortality. With regard to RP-ILD, analyses showed that potential predictors at baseline included age >50 years [HR 2.640 (95% CI 1.277, 5.455)], LDH >300 IU/l [HR 3.189 (95% CI 1.469, 6.918)], fever [HR 1.903 (95% CI 0.956, 3.790)] and neutrophil:lymphocyte ratio >7.0 [HR 1.967 (95% CI 0.942, 4.107)]. We proposed a prediction model based on fever, LDH, age and white cell count (FLAW) to stratify the risk of development of RP-ILD. The probability of RP-ILD in a patient with a score of 4 was 100%. A small internal validation cohort showed the odds of RP-ILD with FLAW scores of 0, 1, 2 and 3 were 0%, 0%, 42.9% and 75%, respectively. CONCLUSIONS: Anti-MDA5-associated RP-ILD is significantly associated with poor survival rates. The FLAW model maybe useful to predict the development of RP-ILD.

Exploring the Genetic and Environmental Etiologies of Phonological Awareness, Morphological Awareness, and Vocabulary Among Chinese-English Bilingual Children: The Moderating Role of Second Language Instruction.

This study investigated the associations among bilingual phonological awareness, morphological awareness, and vocabulary by focusing on their genetic and environmental etiologies. It also explored the influence of family socio-economic status (SES) and language exposure amount on the genetic and environmental effects. A twin study was conducted with 349 pairs of Chinese-English bilingual twins (mean age = 7.37 years). Cross-language transfer was found in phonological and morphological awareness but not in vocabulary knowledge. A common genetic overlap was found among these bilingual abilities. We also found a common shared environmental effect that may account for the cross-language transfer in phonological awareness and the associations among English abilities. SES and language exposure were significant environmental influences on bilingual phonological awareness and English vocabulary. More teaching in Chinese was related to a stronger genetic effect on Chinese morphological awareness, whereas more teaching in English was related to a stronger environmental impact on English abilities.

Cutaneous metastasectomy: Is there a role in breast cancer? A systematic review and overview of current treatment modalities.

Cutaneous metastases (CM) are neoplastic lesions involving the dermis or subcutaneous tissues, originating from another primary tumor. Breast cancer is commonest primary solid tumor, representing 24%-50% of CM patients. There is no "standard of care" on management. In particular, the role of surgery in the treatment of cutaneous metastases from breast carcinoma (CMBC) remains controversial. This systematic review evaluates the role of cutaneous metastasectomy in breast cancer and provides an overview of existing treatment types.

Short Stay Management of Locally Advanced Breast Cancer Using Immediate Local Thoracoabdominal Advancement Flap and Enhanced Recovery After Surgery Protocol.

BACKGROUND: Patients with locally advanced invasive breast cancer (LABC) are often considered inoperable, because of the anticipated chest wall defect and need for complex reconstruction. We present a series of patients who underwent mastectomy with extensive skin resection and immediate chest wall reconstruction using a local thoracoabdominal advancement flap (TAAF). All patients were managed after surgery with an ERAS (Enhanced Recovery After Surgery) protocol, to decrease length of stay in hospital. We also present 1 patient who subsequently had satisfactory bilateral delayed breast reconstruction with pedicled latissimus dorsi myocutaneous flaps with prepectoral silicone implants. METHODS: This is a single-surgeon, single-institution retrospective chart review of patients with LABC who underwent mastectomy with skin resection and local TAAF from May 2017 to October 2019, with minimum 3-month follow-up. RESULTS: Thirteen patients met inclusion criteria. Twelve of 13 patients presented with stage III or IV invasive breast cancer, with skin involvement. The mean chest wall defect measured 248.7 cm2 (140-336 cm2; SD, 63.2 cm2), and all were successfully reconstructed with immediate local TAAF. There were no intraoperative complications, but 1 patient developed a postop hematoma. The mean hospital stay was 1.3 nights, with 9 patients (69.2%) staying less than 23 hours and 4 patients (30.8%) staying 2 nights. Nine patients (69.2%) underwent adjuvant therapy, beginning on average 32 days (13-55 days; SD, 13.1 days) after surgery. The mean follow-up time was 13.8 months (4.5-31.6 months; SD, 9.2 months). One patient underwent successful delayed bilateral breast reconstruction with pedicled latissimus dorsi myocutaneous flaps and silicone implant placement. CONCLUSIONS: Our study demonstrates that reconstruction with local TAAF is an outpatient procedure that reliably provides durable, immediate chest wall coverage, after mastectomy in patients with LABC. This technique has a short operative time, low blood loss, and low complication rate, allowing timely adjuvant therapy. Using an ERAS postop protocol we were able to reduce mean hospital stay to 1.3 days. Compared with other described techniques of reconstruction, the additional scars and donor site morbidity are minimal, allowing for delayed breast reconstruction. We also present survival outcomes data on these surgically managed patients.

Remediation of arsenic-contaminated paddy field by a new iron oxidizing strain (Ochrobactrum sp.) and iron-modified biochar.

Iron-oxidizing strain (FeOB) and iron modified biochars have been shown arsenic (As) remediation ability in the environment. However, due to the complicated soil environment, few field experiment has been conducted. The study was conducted to investigate the potential of iron modified biochar (BC-FeOS) and biomineralization by a new found FeOB to remediate As-contaminated paddy field. Compared with the control, the As contents of GB (BC-FeOS), GF (FeOB), GFN (FeOB and nitrogen fertilizer), GBF (BC-FeOS and FeOB) and GBFN (BC-FeOS, FeOB and nitrogen fertilizer) treatments in pore water decreased by 36.53%-80.03% and the microbial richness of iron-oxidizing bacteria in these treatments increased in soils at the rice maturation stage. The concentrations of available As of GB, GF, GFN, GBF and GBFN at the tillering stage were significantly decreased by 10.78%-55.48%. The concentrations of nonspecifically absorbed and specifically absorbed As fractions of GB, GF, GFN, GBF and GBFN in soils were decreased and the amorphous and poorly crystalline hydrated Fe and Al oxide-bound fraction was increased. Moreover, the As contents of GB, GF, GFN, GBF and GBFN in rice grains were significantly decreased (*P < 0.05) and the total As contents of GFN, GBF and GBFN were lower than the standard limit of the National Standard for Food Safety (GB 2762-2017). Compared with the other treatments, GBFN showed the greatest potential for the effective remediation of As-contaminated paddy fields.

[Chemical constituents from Urtica dioica fruits].

The chemical constituents in Urtica dioica fruits were investigated by silica gel chromatography, preparative HPLC, NMR, and HR-MS for the first time. As a result, 21 compounds were isolated from the fruits of U. dioica and identified 7R,8S,8'R-olivil(1), oleic acid(2), α-linoleic acid(3), palmic acid(4), methyl palmitate(5), α-linolenic acid(6), α-linolenic acid methyl ester(7), 5-O-caffeoyl-shikimic acid(8), vanillic acid(9), p-coumaric acid(10), 5-O-p-coumaroylshikimic acid(11), cinnamic acid(12), quinic acid(13), shikimic acid(14), ethyl caffeate(15), coniferyl ferulate(16), ferulic acid(17), caffeic acid(18), chlorogenic acid(19), pinoresinol(20), and quercetin(21). Compound 1 was a new compound and compounds 2-16 were isolated from U. dioica for the first time.

Simplifying prediction of disease progression in pre-symptomatic type 1 diabetes using a single blood sample.

AIMS/HYPOTHESIS: Accurate prediction of disease progression in individuals with pre-symptomatic type 1 diabetes has potential to prevent ketoacidosis and accelerate development of disease-modifying therapies. Current tools for predicting risk require multiple blood samples taken during an OGTT. Our aim was to develop and validate a simpler tool based on a single blood draw. METHODS: Models to predict disease progression using a single OGTT time point (0, 30, 60, 90 or 120 min) were developed using TrialNet data collected from relatives with type 1 diabetes and validated in independent populations at high genetic risk of type 1 diabetes (TrialNet, Diabetes Prevention Trial-Type 1, The Environmental Determinants of Diabetes in the Young [1]) and in a general population of Bavarian children who participated in Fr1da. RESULTS: Cox proportional hazards models combining plasma glucose, C-peptide, sex, age, BMI, HbA1c and insulinoma antigen-2 autoantibody status predicted disease progression in all populations. In TrialNet, the AUC for receiver operating characteristic curves for models named M60, M90 and M120, based on sampling at 60, 90 and 120 min, was 0.760, 0.761 and 0.745, respectively. These were not significantly different from the AUC of 0.760 for the gold standard Diabetes Prevention Trial Risk Score, which requires five OGTT blood samples. In TEDDY, where only 120 min blood sampling had been performed, the M120 AUC was 0.865. In Fr1da, the M120 AUC of 0.742 was significantly greater than the M60 AUC of 0.615. CONCLUSIONS/INTERPRETATION: Prediction models based on a single OGTT blood draw accurately predict disease progression from stage 1 or 2 to stage 3 type 1 diabetes. The operational simplicity of M120, its validity across different at-risk populations and the requirement for 120 min sampling to stage type 1 diabetes suggest M120 could be readily applied to decrease the cost and complexity of risk stratification.

Rhizosphere bacterial community composition affects cadmium and arsenic accumulation in rice (Oryza sativa L.).

Cadmium (Cd) and arsenic (As) contamination in paddy soils poses serious health risks to humans. The accumulation of Cd and As in rice (Oryza sativa L.) depends on their bioavailability, which is affected by soil physicochemical properties and soil microbial activities. However, little is known about the intricate interplay between rice plants and their rhizosphere microbes during the uptake of Cd and As. In this study, different bacterial communities were established by sterilizing paddy soils with γ-radiation. A pot experiment using two paddy soils with different levels of contamination was conducted to explore how the bacterial community composition affects Cd and As accumulation in rice plants. The results showed that the sterilization treatment substantially changed the bacterial composition in the rhizosphere, and significantly increased the grain yield (by 33.5-38.3%). The sterilization treatment resulted in significantly decreased concentrations of Cd (by 18.2-38.7%) and As (by 20.3-36.7%) in the grain, straw, and root of rice plants. The accumulation of Cd and As in rice plants was negatively correlated with the relative abundance of sulfate-reducing bacteria and iron-oxidizing bacteria in the rhizosphere. Other specific taxa associated with the accumulation of Cd and As in rice plants were also identified. Our results suggest that regulating the composition of the rhizosphere bacterial community could simultaneously reduce Cd and As accumulation in rice grain and increase the grain yield. These results would be useful for developing strategies to cultivate safe rice crops in areas contaminated with Cd and As.

Rectovaginal Fistula Repair 1 Year Later: Lessons Learned.

INTRODUCTION: Rectovaginal (RV) fistulas are notoriously difficult to treat. Various methods for repair exist, and refinements in techniques can lead to "successful" outcomes. Review of the literature demonstrates that outcomes studies are scarce and mostly limited to comments on closure rate. We have experienced "success" in our own series with 100% closure rate, regardless of fistula etiology and comorbidities (radiation, inflammation, etc). However, long-term outcomes, including various complications and quality of life changes, have previously been underreported. METHODS: Critical analysis of various outcomes after fistula repair in 14 patients was performed. Patients were surveyed and interviewed with regard to problems before and after fistula repair to obtain objective data focusing on their experience and outcomes. Conclusions are based on physician assessment and patient surveys 1 year after fistula repair and at least 6 months after ostomy reversal and are discussed within the context of data from the literature. RESULTS: Overall satisfaction rate after repairs was high. All patients would undergo attempt at repair again regardless of complications or functional changes (not present before repair). After repair, sexual dyspareunia affected 5 patients (36%); however, most abstained from sexual activity when their RV fistula became apparent. No patient admitted to dyspareunia before the development of their RV fistula. Anal sphincter and defecation function, as well as stool continence, were judged by surgeons and patients uniformly as adequate. However, 3 patients (21%) complained of intermittent problems with urination. A new/different type of pain affected 2 of 4 patients with Crohn disease. One of these patients subsequently developed a new postsphincteric RV fistula. Another patient noted new intermittent vaginal discharge after ostomy reversal, and magnetic resonance imaging suggested a residual fistula, which was not seen on follow-up sigmoidoscopy and "Blue Dye Test." CONCLUSIONS: We previously reported on algorithms for repair and refinements in techniques for "successful" repair of RV fistulas with zero recurrence rate. Long-term follow-up indicates, however, that although the overall satisfaction rate after surgery is high, true "success," defined as permanent fistula closure, is not necessarily problem free. Long-term morbidity and the management of other unique sequelae and problems are underreported.

Contraception and Pre-Conception Counselling in Cardiac Patients: We Can Do Better. Experience From a Tertiary Centre in New Zealand.

BACKGROUND: Physiological changes in pregnancy can precipitate decompensation in women with pre-existing cardiac disease leading to suboptimal fetal outcome in addition to maternal risk. Many women born with congenital heart disease are living into childbearing years, and rheumatic heart disease (RHD) remains a significant problem within Maori and Pasifika communities in New Zealand. AIMS: To assess documentation of contraception advice and pre-conception counselling in women with pre-existing cardiac disease of childbearing potential and to explore potential barriers to these conversations. METHODS: We conducted a retrospective review of electronic clinic letters of 194 women with modified World Health Organization (mWHO) class 2 or above heart disease. This was followed by a survey of our cardiology team. RESULTS: Fifty-one (51) women with RHD and 143 women with non-RHD were identified. Thirty-eight per cent (38%) of women had documented discussions about contraception and pre-conception counselling. Women with RHD were less likely to receive discussions about contraception than women with non-RHD. All surveyed members of our cardiology team agreed that women with cardiac disease should have planned pregnancies and the majority reported always or usually discussing contraception. Factors such as lack of time, cultural barriers and presence of family members were identified. Many felt that the subject was outside of their expertise or admitted that they simply did not think about it. CONCLUSIONS: Advice regarding contraception in addition to pre-pregnancy counselling should be given to all patients with pre-existing cardiovascular disease of potential child-bearing potential. Our study shows much room for improvement.

Effects of Fe-oxidizing bacteria (FeOB) on iron plaque formation, As concentrations and speciation in rice (Oryza sativa L.).

Large areas of the paddy fields in South China are contaminated with arsenic (As), which causes serious problems, including high As concentrations in brown rice. Three As-resistant iron-oxidizing bacteria (FeOB) namely, Bacillus sp. T2, Pseudomonas sp. Yangling I4 and Bacillus sp. TF1-3, were isolated and applied to rice grown in different As-contaminated environments to study the effects of FeOB on the As accumulation in rice and clarify the possible mechanisms involved. The results showed that FeOB inoculation significantly decreased the inorganic As concentrations in brown rice grown in pots and paddy fields by 3.7-13.3% and 4.6-12.1%, respectively. FeOB inoculation enhanced the formation of Fe plaque, which sequestered more As on the root surface. Moreover, a significantly lower level of As(III) influx was observed in the rice cultivated with FeOB than in the control. FeOB inoculation also decreased the As concentrations in pore water and the Fe(II)/Fe(III) ratio in rhizosphere soil. The present results suggest that FeOB inoculation decreased the inorganic As concentrations in brown rice by affecting the formation of Fe plaque, As(III) uptake kinetics and rhizosphere soil properties. Based on our results, FeOB inoculation could be considered a useful method to decrease inorganic As concentrations in brown rice grown in As-contaminated paddy fields.

Interplay of Prenatal and Postnatal Risk Factors in the Behavioral and Histological Features of a "Two-Hit" Non-Genetic Mouse Model of Schizophrenia.

Schizophrenia is a multifactorial developmental neuropsychiatric disorder. This study examined the interplay of maternal infection and postweaning social isolation, which are prenatal and postnatal risk factors, respectively. Pregnant mice received poly I:C or saline injection on gestation day 9 and the pups were weaned at postnatal day 28. After weaning, male offspring were randomly assigned into group-rearing and isolation-rearing groups. In their adulthood, we performed behavioral tests and characterized the histochemical features of their mesocorticolimbic structures. The sociability and anxiety levels were not affected by either manipulation, but synergistic effects of the two hits on stress-coping behavior was observed. Either of the single manipulations caused defects in sensorimotor gating, novel object recognition and spatial memory tests, but the combination of the two hits did not further exacerbate the disabilities. Prenatal infection increased the number of dopaminergic neurons in midbrain, whereas postweaning isolation decreased the GABAergic neurons in cortex. Single manipulation reduced the dendritic complexity and spine densities of neurons in the medial prefrontal cortex (mPFC) and dentate gyrus. Our results support the current perspective that disturbances in brain development during the prenatal or postnatal period influence the structure and function of the brain and together augment the susceptibility to mental disorders, such as schizophrenia.