Large-scale genomic investigation of pediatric cholestasis reveals a novel hepatorenal ciliopathy caused by PSKH1 mutations.

PURPOSE: Pediatric cholestasis is the phenotypic expression of clinically and genetically heterogeneous disorders of bile acid synthesis and flow. Although a growing number of monogenic causes of pediatric cholestasis have been identified, the majority of cases remain undiagnosed molecularly. METHODS: In a cohort of 299 pediatric participants (279 families) with intrahepatic cholestasis, we performed exome sequencing as a first-tier diagnostic test. RESULTS: A likely causal variant was identified in 135 families (48.56%). These comprise 135 families that harbor variants spanning 37 genes with established or tentative links to cholestasis. In addition, we propose a novel candidate gene (PSKH1) (HGNC:9529) in 4 families. PSKH1 was particularly compelling because of strong linkage in 3 consanguineous families who shared a novel hepatorenal ciliopathy phenotype. Two of the 4 families shared a founder homozygous variant, whereas the third and fourth had different homozygous variants in PSKH1. PSKH1 encodes a putative protein serine kinase of unknown function. Patient fibroblasts displayed abnormal cilia that are long and show abnormal transport. A homozygous Pskh1 mutant mouse faithfully recapitulated the human phenotype and displayed abnormally long cilia. The phenotype could be rationalized by the loss of catalytic activity observed for each recombinant PSKH1 variant using in vitro kinase assays. CONCLUSION: Our results support the use of genomics in the workup of pediatric cholestasis and reveal PSKH1-related hepatorenal ciliopathy as a novel candidate monogenic form.

Ppb-Level Hydrogen Sulfide Gas Sensor Based on the Nanocomposite of MoS2 Octahedron/ZnO-Zn2SnO4 Nanoparticles.

Hydrogen sulfide (H2S) detection is extremely necessary due to its hazardous nature. Thus, the design of novel sensors to detect H2S gas at low temperatures is highly desirable. In this study, a series of nanocomposites based on MoS2 octahedrons and ZnO-Zn2SnO4 nanoparticles were synthesized through the hydrothermal method. Various characterizations such as X-ray diffraction (XRD), Brunauer-Emmett-Teller (BET), scanning electron microscopy (SEM), transmission electron microscopy (TEM), energy-dispersive X-ray spectroscopy (EDS) and X-ray photoelectron spectrum (XPS) have been used to verify the crystal phase, morphology and composition of synthesized nanocomposites. Three gas sensors based on the nanocomposites of pure ZnO-Zn2SnO4 (MS-ZNO-0), 5 wt% MoS2-ZnO-Zn2SnO4 (MS-ZNO-5) and 10 wt% MoS2-ZnO-Zn2SnO4 (MS-ZNO-10) were fabricated to check the gas sensing properties of various volatile organic compounds (VOCs). It showed that the gas sensor of (MS-ZNO-5) displayed the highest response of 4 to 2 ppm H2S and fewer responses to all other tested gases at 30 °C. The sensor of MS-ZNO-5 also displayed humble selectivity (1.6), good stability (35 days), promising reproducibility (5 cycles), rapid response/recovery times (10 s/6 s), a limit of detection (LOD) of 0.05 ppm H2S (Ra/Rg = 1.8) and an almost linear relationship between H2S concentration and response. Several elements such as the structure of MoS2, higher BET-specific surface area, n-n junction and improvement in oxygen species corresponded to improving response.

H2S/Butane Dual Gas Sensing Based on a Hydrothermally Synthesized MXene Ti3C2Tx/NiCo2O4 Nanocomposite.

Real-time sensing of hydrogen sulfide (H2S) at room temperature is important to ensure the safety of humans and the environment. Four kinds of different nanocomposites, such as MXene Ti3C2Tx, Ti3AlC2, WS2, and MoSe2/NiCo2O4, were synthesized using the hydrothermal method in this paper. Initially, the intrinsic properties of the synthesized nanocomposites were studied using different techniques. P-type butane and H2S-sensing behaviors of nanocomposites were performed and analyzed deeply. Four sensor sheets were fabricated using a spin-coating method. The gas sensor was distinctly part of the chemiresistor class. The MXene Ti3C2Tx/NiCo2O4-based gas sensor detected the highest response (16) toward 10 ppm H2S at room temperature. In comparison, the sensor detected the highest response (9.8) toward 4000 ppm butane at 90 °C compared with the other three fabricated sensors (Ti3AlC2, WS2, and MoSe2/NiCo2O4). The MXene Ti3C2Tx/NiCo2O4 sensor showed excellent responses, minimum limits of detection (0.1 ppm H2S and 5 ppm butane), long-term stability, and good reproducibility compared with the other fabricated sensors. The highest sensing properties toward H2S and butane were accredited to p-p heterojunctions, higher BET surface areas, increased oxygen species, etc. These simply synthesized nanocomposites and fabricated sensors present a novel method for tracing H2S and butane at the lowest concentration to prevent different gas-exposure-related diseases.

Persistent Müllerian Duct Syndrome Diagnosed Incidentally: A Case Report.

Persistent Müllerian Duct syndrome is a rare male disorder of sexual development. The phenotypically and genotypically male patient presents with female internal organs (i.e., uterus, cervix, fallopian tubes and upper part of vagina) due to deficiency of anti-mullerian hormone or insensitivity of tissues to Anti Mullerian Hormone. We present a 19 year old male who came with complaint of right iliac fossa pain. He was investigated for acute appendicitis and on imaging, he was diagnosed to have bilateral cryptorchidism with rudimentary uterus. Computed tomography followed by pelvic ultrasonography was done which indicated two testes in abdomen and a soft tissue density structure, identified as a rudimentary uterus located posterior to the urinary bladder. CT scan findings were further confirmed by magnetic resonance imaging pelvis. A trial of stepwise orchidopexy followed by orchidectomy with removal of rudimentary uterus was performed laparoscopically. Additionally, he was counselled for long term sex hormone replacement and reproductive failure in future.

Multi-target mechanism of Solanum xanthocarpum for treatment of psoriasis based on network pharmacology and molecular docking.

Solanum xanthocarpum (SX) has been used to treat a variety of diseases, including skin disorders like psoriasis (PSO). SX possesses many pharmacological activities of anti-inflammatory, anti-cancer, immunosuppressive, and healing qualities. However, the multi-target mechanism of SX on PSO still needs clarity. Materials and methods: The Indian Medicinal Plants, Phytochemicals and Therapeutics (IMPPAT) database and the Swiss Target Prediction online tool were used to find the active phytochemical components and their associated target proteins. OMIM and GeneCards databases were used to extract PSO-related targets. A Venn diagram analysis determined the common targets of SX against PSO. Subsequently, the protein-protein interaction (PPI) network and core PPI target analysis were carried out using the STRING network and Cytoscape software. Also, utilising the online Metascape and bioinformatics platform tool, a pathway enrichment analysis of common targets using the Kyoto Encyclopaedia of Genes and Genome (KEGG) and Gene Ontology (GO) databases was conducted to verify the role of targets in biological processes, cellular components and molecular functions with respect to KEGG pathways. Lastly, molecular docking simulations were performed to validate the strong affinity between components of SX and key target receptors. Results: According to the IMPPAT Database information, 8 active SX against PSO components were active. According to the PPI network and core targets study, the main targets against PSO were EGFR, SRC, STAT3, ERBB2, PTK2, SYK, EP300, CBL, TP53, and AR. Moreover, molecular docking simulations verified the binding interaction of phytochemical SX components with their PSO targets. Last but not least, enrichment analysis showed that SX is involved in several biological processes, including peptidyl-tyrosine phosphorylation, peptidyl-tyrosine modification, and peptidyl-serine modification. The relevant KEGG signalling pathways are the PI3K-AKT signalling pathway, the EGFR tyrosine kinase inhibitor resistance pathway, and the MAPK signalling pathway. Conclusion: The network pharmacology technique, which is based on data interpretation and molecular docking simulation techniques, has proven the multi-target function of SX phytoconstituents.

HIV-HCV Coinfection: Prevalence and Treatment Outcomes in Malaysia.

BACKGROUND: Around 130 million infections of hepatitis C virus with 3% overall prevalence are there worldwide. There are approximately 4-5 million persons coinfected with HIV. The main objectives of this study were to determine the prevalence of HCV among HIV-positive individuals and to assess the predictors involved in the outcomes of HIV-HCV coinfected patients. METHODS: A retrospective, cross-sectional study was conducted on patients enrolled from 2007 to 2012 at Infectious Disease Unit, Hospital Palau Pinang, Pinang, Malaysia. Sociodemographic da%)ta as well as clinical data were collected with the help of a valid data collection form from the patients' records. Data were entered and analyzed by using statistical software SPSS version 20.0, and p < 0.05 was considered significant. RESULTS: The overall prevalence of hepatitis C among 708 HIV-infected patients was 130 (16.1 including 541 (76.4%) males and 167 (23.6%) females. High prevalence of HIV-HCV coinfection was significantly observed in males (122 [17.2%]) compared to females (8 [1.1%]) (p < 0.001). The main route of transmission among HIV-HCV coinfected patients was heterosexual contact (98 [13.8%]), followed by homosexual contact (4 [0.4%]). The statistically significant predictors involved in treatment outcomes of HIV-HCV coinfected patients are gender (OR = 2.015, p = 0.002) and intravenous drug users (OR = 2.376, p ≤ 0.001). CONCLUSION: The current study shows that HCV infection has an impact on the recovery of CD4 cells of the patients on HAART. Screening of HCV among HIV patients who were smokers and intravenous drug users should be monitored before starting HAART.

Response Surface Methodology (RSM)-Based Optimization of Ultrasound-Assisted Extraction of Sennoside A, Sennoside B, Aloe-Emodin, Emodin, and Chrysophanol from Senna alexandrina (Aerial Parts): HPLC-UV and Antioxidant Analysis.

In this study, ultrasound-assisted extraction conditions were optimized to maximize the yields of sennoside A, sennoside B, aloe-emodin, emodin, and chrysophanol from S. alexandrina (aerial parts). The three UAE factors, extraction temperature (S1), extraction time (S2), and liquid to solid ratio (S3), were optimized using response surface methodology (RSM). A Box-Behnken design was used for experimental design and phytoconstituent analysis was performed using high-performance liquid chromatography-UV. The optimal extraction conditions were found to be a 64.2 °C extraction temperature, 52.1 min extraction time, and 25.2 mL/g liquid to solid ratio. The experimental values of sennoside A, sennoside B, aloe-emodin, emodin, and chrysophanol (2.237, 12.792, 2.457, 0.261, and 1.529%, respectively) agreed with those predicted (2.152, 12.031, 2.331, 0.214, and 1.411%, respectively) by RSM models, thus demonstrating the appropriateness of the model used and the accomplishment of RSM in optimizing the extraction conditions. Excellent antioxidant properties were exhibited by S. alexandrina methanol extract obtained using the optimized extraction conditions with a DPPH assay (IC50 = 59.7 ± 1.93, µg/mL) and ABTS method (47.2 ± 1.40, µg/mL) compared to standard ascorbic acid.

Box-Behnken Design (BBD)-Based Optimization of Microwave-Assisted Extraction of Parthenolide from the Stems of Tarconanthus camphoratus and Cytotoxic Analysis.

Parthenolide, a strong cytotoxic compound found in different parts of Tarchonanthus camphoratus which motivated the authors to develop an optimized microwave-assisted extraction (MEA) method using Box-Behnken design (BBD) for efficient extraction of parthenolide from the stem of T. camphoratus and its validation by high-performance thin-layer chromatography (HPTLC) and cytotoxic analysis. The optimized parameters for microwave extraction were determined as: 51.5 °C extraction temperature, 50.8 min extraction time, and 211 W microwave power. A quadratic polynomial model was found the most suitable model with R2 of 0.9989 and coefficient of variation (CV) of 0.2898%. The high values of adjusted R2 (0.9974), predicted R2 (0.9945), and signal-to-noise ratio (74.23) indicated a good correlation and adequate signal, respectively. HPTLC analyzed the parthenolide (Rf = 0.16) content in T. camphoratus methanol extract (TCME) at λmax = 575 nm and found it as 0.9273% ± 0.0487% w/w, which was a higher than expected yield (0.9157% w/w). The TCME exhibited good cytotoxicity against HepG2 and MCF-7 cell lines (IC50 = 30.87 and 35.41 µg/mL, respectively), which further supported our findings of high parthenolide content in TCME. This optimized MAE method can be further applied to efficiently extract parthenolide from marketed herbal supplements containing different Tarconanthus species.

Clinical efficacy of scaling and root planing with and without metronidazole on glycemic control: three-arm randomized controlled trial.

BACKGROUND: Treating periodontitis through non-surgical periodontal therapy (NSPT) may improve glycemic control in type-2 Diabetes Mellitus (T2DM) patients. However, the evidence to maintain this improvement beyond four months is insufficient. Hence, this trial was conducted to assess clinical efficacy of NSPT on glycemic control in T2DM patients. METHODS: This three-arm randomized controlled trial recruited 150 known T2DM participants (35-65 years), suffering from moderate to severe periodontitis, having HbA1c level ≥ 6.5% at baseline. Participants were followed up at 3 and 6 months. Intervention for test group-1 included scaling and root planing (SRP) with metronidazole (MET) and oral hygiene instructions (OHI). Test group-2 was intervened with SRP + OHI and control group with OHI only. Stata v. 14 was used to observe inter and intragroup mean changes in glycemic [glycated hemoglobin (HbA1c), fasting blood glucose (FBG)] and periodontal variables [bleeding on probing (BOP), periodontal pocket depth (PPD), clinical attachment loss (CAL)] using ANOVA and RMANOVA. Proportion of change in outcome variable (HbA1c) was assessed between treatment groups using chi-square test. Change was considered significant at p-value ≤ 0.05. RESULTS: A significant reduction was observed in BOP, PPD, CAL, HbA1c and FBG over time [p < 0.05]. Significant reductions were observed in same variables in both test groups in comparison to control arm [p < 0.05]. No change between the two test groups was observed [p > 0.05]. CONCLUSION: Scaling and root planing improves glycemic control of T2DM patients independently of the use of MET. Therefore, SRP after every 6 months may be suggested and included as a part of overall diabetes management for patients suffering from T2DM. Clinical trial registration NCT 03,343,366 [Date of Registration: 17/11/2017].

Evaluation of HbA1c in type-2 diabetes mellitus patients with periodontitis: preliminary findings of three-arm clinical trial.

OBJECTIVE: To assess a relationship and predict changes in glycaemic control due to chronic periodontitis in type-2 diabetic patients. METHODS: Chronic periodontitis (CP) of a cross-section of 118 patients (age ?32 years) was determined using bleeding on probing (BOP), periodontal pocket depth (PPD) and clinical attachment loss (CAL). Their HbA1c, fasting blood glucose (FBG), fasting serum insulin (FSI) and homeostasis assessment model of insulin resistance (HOMA-IR) levels were also tested. Stata 11.0 was used to assess correlation between periodontal and glycaemic measures. Univariate analysis followed by multiple regression analysis through stepwise forward selection process was used to explore significant variables that may predict change in HbA1c. Multi-collinearity and heteroskedasticity were assessed at p-value > 0.05. RESULTS: Results of participants (n=95) showed significantly positive correlations (r) between HbA1c and BOP [r = 0.34, p-value = 0.002], PPD [r = 0.36, p-value = 0.003] and CAL [r=0.42, p-value = 0.002]. However, FBG and HOMA-IR were not found correlated with any of the periodontal measures; except CAL with FBG [r=0.27, p-value=0.02]. In addition to healthy controlled diet, cultural background, education and FBG, CAL was found significant [coef. = 0.746, p-value = 0.001, CI = 0.339, 1.153] to predict change in HbA1c in the final model [R2 = 0.549, p-value < 0.001] with no multicollinearity [mean VIF =1.30] and heteroskedasticity [chi 2 =0.02, p-value= 0.878] in fi n al model. CONCLUSIONS: Increased CAL is estimated to increase HbA1c level by 0.75% in T2DM patients after controlling other factors. It is suggested that periodontal prophylactic management may be planned with an aim to reduce HbA1c. CLINICAL TRIAL REGISTRATION NO: NCT03343366.

Nutritional hypophosphatemic rickets secondary to Neocate® use.

Elemental formula is commonly used in children with feeding intolerance. We describe two, medically complex and feeding tube dependent, patients exclusively fed with Neocate® who subsequently developed hypophosphatemic rickets. Both patients had gross motor decline and pain with physical touch. They were found to have low serum phosphorus, normal calcium, and vitamin D studies, with elevated alkaline phosphatase suggestive of nutritional hypophosphatemia. Both courses were complicated by hypocalcemia following formula change and phosphorus supplementation, highlighting the need for careful management of phosphate repletion in affected individuals. Diligent serial electrolyte monitoring as well as attention to bone health is needed in conjunction with elemental nutrition. Formula change led to restoration of calcium and phosphorus homeostasis and radiographic improvement in these patients.

Evaluating RANKL and OPG levels in patients with Duchenne muscular dystrophy.

RANKL-OPG should be explored in DMD patients to potentially provide targeted therapy. We quantified RANKL and OPG levels in DMD patients compared with controls. RANKL, OPG, and RANKL:OPG significantly declined with age in DMD patients suggesting some bone turnover markers are difficult to assess or use as therapeutic indicators. INTRODUCTION: Osteoporosis in Duchenne muscular dystrophy (DMD) is multi-factorial in nature with high prevalence of fractures. RANKL-OPG should be explored to potentially provide targeted therapy for these patients. We quantified RANKL, OPG, and RANKL:OPG levels in DMD patients compared with controls and analyzed the influence of age, glucocorticoid use, ambulatory status, bone density, and fracture history. METHODS: DMD patients were enrolled at CHLA. Controls were recruited from general pediatric clinic and in collaboration with samples from a previously completed study. Free soluble RANKL and OPG levels were quantified using a sandwich ELISA. RESULTS: Fifty DMD patients and 50 controls were enrolled. DMD patients had a significant decline in RANKL, OPG, and RANKL:OPG with age (p = < 0.0001, p = 0.026, and p = 0.002, respectively) while healthy controls showed no significant change. RANKL trended lower in patients on glucocorticoids (p = 0.05), attributed to the significantly older age in the treatment group. RANKL and RANKL:OPG levels were significantly lower in the non-ambulatory group compared with the ambulatory group (p = 0.010 and 0.036 respectively), again likely due to their older age. There was no correlation of RANKL, OPG, or RANKL:OPG with DXA Z-score or presence of vertebral fractures. CONCLUSION: There was significant decline in RANKL, OPG, and RANKL:OPG with age in DMD patients compared with controls, potentially due to disease severity or worsening osteoblastic function. This suggests some bone turnover markers may be difficult to assess or use as therapeutic indicators in DMD patients. Larger studies are needed to evaluate the role of RANKL-OPG in DMD patients to provide better targeted therapy.

Bisphosphonate therapy in an infant with generalized arterial calcification with an ABCC6 mutation.

Generalized arterial calcification of infancy (GACI) is a rare genetic disorder with high infantile mortality, described to be due to ENPP1, and less commonly ABCC6 mutations. Bisphosphonate treatment has been described to improve survival in ENPP1-positive GACI patients, but few studies have described bisphosphonate treatment in ABCC6-positive patients. Without therapy, patients will die before 6 months of age. Our patient is now 3 years old, former recipient twin of twin-to-twin transfusion syndrome (TTTS). Initial fetal echocardiogram at 19 weeks showed calcifications of the ascending aorta and pulmonary artery (PA). She underwent utero laser therapy, and despite resolution of the TTTS, her follow-up scans showed progressive calcification of the aorta and PA. Postnatal echocardiogram showed calcification and supravalvar stenosis of the aorta and PA. CT on day of life 6 showed calcifications in the PAs, aortic arch, and descending aorta. Quantification of valvular calcification can be difficult; in our patient, increasing outflow tract gradient on echocardiogram was used to monitor disease progression. Molecular testing revealed an ABCC6 gene mutation. She was started on weekly IV pamidronate (0.1-0.3 mg/kg/week) on day 8 of life then transitioned to oral etidronate (15-20 mg/kg/day). Given progressive supravalvar aortic and pulmonary stenosis, she underwent surgical repair with patch augmentation of the PA and ascending aorta at 4 months old. She has done well post-operatively, continuing on enteral bisphosphonate therapy with no side effects to date. Her identical twin was confirmed to have the same mutation and remains asymptomatic with no calcifications. Aggressive bisphosphonate therapy should be started as soon as possible in patients with infantile arterial calcinosis due to ABCC6 or ENPP1 mutations. Echocardiographic evaluation can be used to monitor disease progression by arterial gradients. Molecular testing is also essential to evaluate for possible co-morbidities in these patients and pregnancy management for the future.

Transcriptional modulator ZBED6 affects cell cycle and growth of human colorectal cancer cells.

The transcription factor ZBED6 (zinc finger, BED-type containing 6) is a repressor of IGF2 whose action impacts development, cell proliferation, and growth in placental mammals. In human colorectal cancers, IGF2 overexpression is mutually exclusive with somatic mutations in PI3K signaling components, providing genetic evidence for a role in the PI3K pathway. To understand the role of ZBED6 in tumorigenesis, we engineered and validated somatic cell ZBED6 knock-outs in the human colorectal cancer cell lines RKO and HCT116. Ablation of ZBED6 affected the cell cycle and led to increased growth rate in RKO cells but reduced growth in HCT116 cells. This striking difference was reflected in the transcriptome analyses, which revealed enrichment of cell-cycle-related processes among differentially expressed genes in both cell lines, but the direction of change often differed between the cell lines. ChIP sequencing analyses displayed enrichment of ZBED6 binding at genes up-regulated in ZBED6-knockout clones, consistent with the view that ZBED6 modulates gene expression primarily by repressing transcription. Ten differentially expressed genes were identified as putative direct gene targets, and their down-regulation by ZBED6 was validated experimentally. Eight of these genes were linked to the Wnt, Hippo, TGF-ß, EGF receptor, or PI3K pathways, all involved in colorectal cancer development. The results of this study show that the effect of ZBED6 on tumor development depends on the genetic background and the transcriptional state of its target genes.

HBV and HIV co-infection: Prevalence and clinical outcomes in tertiary care hospital Malaysia.

According to WHO, Malaysia has been classified as a concentrated epidemic country due to progression of HIV infection in the population of injecting drug users. The main objectives of current study are to determine the prevalence of HBV among HIV-positive individuals in a tertiary care hospital of Malaysia and to assess the predictors involved in the outcomes of HIV-HBV co-infected patients. A retrospective, cross-sectional study is conducted at Hospital Palau Pinang, Malaysia. The collection of socio-demographic data as well as clinical data is done with the help of data collection form. Data were analyzed after putting the collected values of required data by using statistical software SPSS version 20.0 and P > 0.05 is considered as significant. Results show that the overall prevalence of HBV was 86 (13%) including 495 (74.5%) males and 169 (25.5%) females among a total of 664 HIV-infected patients. It was observed that there is a high prevalence of HIV-HBV co-infection in males 76 (11.4%) as compared to females 10 (1.5%) (P = 0.002). The median age of the study population was 39 years. The statistical significant risk factors involved in the outcomes of HIV-HBV co-infected patients were observed in the variables of gender, age groups, and injecting drug users. The findings of the present study shows that the prevalence of HBV infection among HIV-positive patients was 13% and the risk factors involved in the outcomes of HIV-HBV co-infected patients were gender, age, and intravenous drug users.

Functional Response of Four Syrphid Predators Associated With Green Apple Aphid (Hemiptera: Aphididae) in Laboratory.

Aphis pomi De Geer, the green apple aphid, is an economic pest of apple and other rosaceae throughout the world. In the present study, functional responses of the syrphids Episyrphus balteatus De Geer, Eristalis tenax(L.), Eristalis interruptus (Poda), and Sphaerophoria scripta (L.), to A. pomi were studied under laboratory conditions to determine their relative predatory potential. The second- and third-instar larvae of the predators were exposed to increasing densities of similar-sized A. pomi nymphs in Petri dishes. Ep. balteatus was found to possess the highest consumption rate followed by Er. tenax, Er. interruptus, and S. scripta. All predator species and stages exhibited a Type II functional response. The coefficients of attack rate and handling time showed an insignificant variation between species and preying stages, suggesting equal potential of the four syrphid species to regulate A. pomi colonies.

Qualitative and quantitative prey requirements of two aphidophagous coccinellids, Adalia tetraspilota and Hippodamia variegata.

The suitability of two prey species, Aphis pomi De Geer (Hemiptera: Aphididae) and Brevicoryne brassicae (L.), for two generalist aphidophagous coccinellids, Adalia tetraspilota (Hope) (Coleoptera: Coccinellidae) and Hippodamia variegata (Goeze), at various abundance levels was investigated under laboratory conditions. While both A. pomi and B. brassicae were found to be suitable, the predators performed better when feeding upon B. brassicae. The prey densities affected the developmental parameters of the two predators appreciably. Optimal growth and development was noted in the prey density range of 40-80 aphids per day per predator. Both species and abundance levels of prey significantly affected the larval period of the two predators. Appreciable variation in survivorship of larvae, prepupal and pupal period, and adult weight was noted by varying the prey species and prey abundance. Longer reproductive period (oviposition period) and shorter non-reproductive periods (preoviposition and postoviposition periods) were noted for females that fed on B. brassicae as compared to those that fed on A. pomi. Reproductive output was appreciably higher for females that fed on B. brassicae, and the fecundity decreased drastically under food shortage.

Risk factors for intraventricular haemorrhage in preterm infants from a tertiary care hospital of Karachi, Pakistan.

OBJECTIVE: To determine the incidence of Intraventricular Haemorrhage in pre-term infants, along with adverse neonatal outcomes associated with the disease. METHODS: The retrospective case control study was conducted at Aga Khan University Hospital, Karachi, and comprised patients' records from January 2004 to December 2009 of preterm babies from 26-35 weeks of gestation who had Intraventricular Haemorrhage of any grade. The diagnosis was confirmed by ultrasound scan. Controls were preterm births matched with the cases according to gestational age (±1 week) and birth weight (±150 grams). SPSS 19 was used for statistical analysis. RESULT: Of the total 201 preterm babies in the study, there were 67(33.33%) cases and 134(66.66%) controls; the respective ratio being 1:2.The incidence of Intraventricular Haemorrhage in the study population was 22.1 per 1000 live births.The odds of developing Intraventricular Haemorrhage was substantially higher in babies with respiratory distress syndrome (odds ratio: 3.77; 95% Confidence Interval: 1.52-9.37; p < 0.004) and who were given mechanical ventilation (odds ratio: 23.6; 95% Confidence Interval: 5.09-109.5; p < 0.001). There was a four-fold increase in risk of Intraventricular Haemorrhage in babies who received surfactant administration (odds ratio: 4.26; 95% Confidence Interval: 1.77-10.22; p < 0.001). Out of 67 cases, 50 (74.6%) re-demonstrated the same grade, 13 (19.4%) were resolved, and 4 (6%) progressed. Overall, there were 38 death; the mortality rate being 56.71. CONCLUSION: The risk of Intraventricular Haemorrhage was substantially higher in preterm neonates with respiratory distress syndrome, etc., and the mortality rate was higher in babies with severe disease.

Forecasting the Pharmacological Mechanisms of Plumbago zeylanica and Solanum xanthocarpum in Diabetic Retinopathy Treatment: A Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation Study.

(1) Background: Diabetic retinopathy (DR) is a major complication of diabetes, marked by abnormal angiogenesis, microaneurysms, and retinal hemorrhages. Traditional Ayurvedic medicine advocates multi-target strategies for DR management. However, the mechanisms by which Solanum xanthocarpum (SX) and Plumbago zeylanica (PZ) exert therapeutic effects are not well understood; (2) Methods: To investigate these mechanisms, we employed network pharmacology and molecular docking techniques. Phytochemicals from SX and PZ were identified using the IMPPAT database and Swiss Target Prediction tool. DR-related protein targets were sourced from the GeneCards database, and common targets were identified through Venn diagram analysis. STRING and Cytoscape were used to construct and analyze protein-protein interaction networks. Pathway enrichment was performed with Gene Ontology and KEGG databases; (3) Results: We identified 28 active phytoconstituents, targeting proteins such as EGFR, SRC, STAT3, AKT1, and HSP90AA1. Molecular docking and dynamics simulations confirmed the strong binding affinities of these compounds to their targets; (4) Conclusions: The study highlights the multi-target activity of SX and PZ, particularly in pathways related to EGFR tyrosine kinase inhibitor resistance and PI3K-AKT signaling. These findings provide valuable insights into their therapeutic potential for DR, suggesting the effective modulation of key molecular pathways involved in the disease.

Uncommon Pathogen: Achromobacter xylosoxidans Infection Following Total Knee Arthroplasty.

Introduction: Achromobacter xylosoxidans is an uncommon opportunistic organism, mainly causing infection in immune-compromised hosts. A. xylosoxidans is a non-fermenting Gram-negative bacillus. Being closely associated with Alcaligenes species was also called A. xylosoxidans. Case Report: A few cases of periprosthetic infection by A. xylosoxidans have been reported outside India. A periprosthetic infection with A. xylosoxidans following a total knee arthroplasty is reported in a female. Conclusion: A. xylosoxidans is a pathogen capable of causing prosthetic joint infection even in immunocompetent patients. Thorough debridement and appropriate antibiotic treatment is essential for the success of revision surgery.