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The development of strategies for targeting the asymptomatic carriage of Salmonella Typhi in chronic typhoid patients has suffered owing to our basic lack of understanding of the molecular mechanisms that enable the formation of S . Typhi biofilms. Traditionally, studies have relied on cholesterol-attached biofilms formed by a closely related serovar, Typhimurium, to mimic multicellular Typhi communities formed on human gallstones. In long-term infections, S . Typhi adopts the biofilm lifestyle to persist in vivo and survive in the carrier state, ultimately leading to the spread of infections via the fecal-oral route of transmission. In the present work, we studied S . Typhi biofilms directly, applied targeted as well as genome-wide genetic approaches to uncover unique biofilm components that do not conform to the CsgD-dependent pathway established in S . Typhimurium. We undertook a genome-wide Tn5 mutation screen in H58, a clinically relevant multidrug resistance strain of S . Typhi, in gallstone-mimicking conditions. We generated New Generation Sequencing libraries based on the ClickSeq technology to identify the key regulators, IraP and RpoS, and the matrix components Sth fimbriae, Vi capsule and lipopolysaccharide. We discovered that the starvation sigma factor, RpoS, was required for the transcriptional activation of matrix-encoding genes in vitro, and for S . Typhi colonization in persistent infections in vivo, using a heterologous fish larval model. An rpoS null mutant failed to colonize the gall bladder in chronic zebrafish infections. Overall, our work uncovered a novel RpoS-driven, CsgD-independent paradigm for the formation of cholesterol-attached Typhi biofilms, and emphasized the role(s) of stress signaling pathways for adaptation in chronic infections. Our identification of the biofilm regulators in S . Typhi paves the way for the development of drugs against typhoid carriage, which will ultimately control the increased incidence of gall bladder cancer in typhoid carriers.

Recent studies suggested that successful clearance of chronic Hepatitis C Virus (HCV) by using direct-acting antiviral (DAA) agents could improve glycemic control in patients with diabetes; however, some studies failed to identify this benefit. We conducted a systematic review and meta-analysis to assess the impact of sustained virologic response (SVR) after treatment with DAA agents on glycemic control. Embase, Scopus and PubMed were searched through March 26th, 2023, for all studies evaluating whether eradication of HCV infection with DAAs is associated with an impact on glycemic control. Only studies with data on glycemic control, including haemoglobin A 1 c (HbA 1 c), fasting glucose, or Homeostatic Model Assessment for Insulin Resistance (HOMA-IR), at least 12-week post-SVR were included. Sixteen studies met our eligibility criteria and were included in qualitative analysis. The mean HbA 1 c was 8.05% (95% CI: 7.79%-8.31%) before treatment and 7.19% (95% CI: 6.98%-7.39%) after treatment. There was a significant mean absolute reduction in HbA1c of 0.72% (95% CI: 0.52%-0.93%) with high heterogeneity between studies (I 2  = 91.7%). The reduction in HbA1c remained significant in the subgroup analysis at 3 months follow up post SVR [0.74% (95% CI: 0.57%-0.91%)] and at least 6 months follow up [0.66% (95% CI: 0.23%-1.10%)]. We found a significant reduction in HbA 1 C after SVR in patients with type 2 diabetes mellitus, reflecting better glycemic control with HCV eradication. This data highlights an important extrahepatic benefit of HCV eradication., (© 2024 John Wiley & Sons Ltd.)

Background and Aims: Fully covered self-expandable metal stents (FCSEMSs) are widely used in benign upper gastrointestinal (GI) conditions, but stent migration remains a limitation. An over-the-scope clip (OTSC) device (Stentfix {SF], Ovesco Endoscopy) for stent anchoring has recently been developed. The aim of this study was to evaluate the effect of OTSC fixation on FCSEMS migration rate., Methods: In this retrospective review of consecutive patients who underwent FCSEMS placement for benign upper GI conditions from January 2011 to October 2022 at 16 centers, the primary outcome was rate of stent migration. The secondary outcomes were clinical success and adverse events., Results: A total of 311 (no fixation [NF] 122, SF 94, endoscopic suturing [ES] 95) patients underwent 316 stenting procedures. Compared with the NF group (n = 49, 39%), the rates of stent migration were significantly lower in the SF (n = 16, 17%, P = .001) and ES (n = 23, 24%, P = .01) groups. The rates of stent migration were not different between the SF and ES groups (P = .2). On multivariate analysis, SF (odds ratio [OR], 0.34, 95% CI, 0.17-0.70, P < .01) and ES (OR, 0.46, 95% CI, 0.23-0.91; P = .02) were independently associated with decreased risk of stent migration. Compared with the NF group (n = 64; 52%), there were higher rates of clinical success in the SF (n = 64; 68%; P = .03) and ES (n = 66; 69%; P = .02) groups. There was no significant difference in the rates of adverse events among the 3 groups., Conclusion: Stent fixation using OTSCs is safe and effective at preventing stent migration and may also result in improved clinical response., Competing Interests: Disclosure The following authors disclosed financial relationships: B. Confer: consultant for Boston Scientific, J.J. Pineda-Bonilla: consultant for Boston Scientific, R. Pawa: consultant for Boston Scientific and Cook Medical, S. Pawa: consultant for Boston Scientific, R.E. Kim: consultant for Boston Scientific and Cook Medical, H.S. Khara: consultant for Boston Scientific, Cook Medical, ConMed, Pentax, Medtronic, and Olympus, G.O. Spaun - consultant for Boston Scientific, K.H. Park: consultant for Olympus, Endorobotics, MicroTech, D.D. Diehl: consultant for Boston Scientific, Micro-Tech, Lumendi, Merit, Pentax, Actuated Medical, Steris, and Olympus, P. Kedia: consultant for Boston Scientific, Medtronic, and Olympus, M.A. Khashab: consultant for Boston Scientific, UpToDate, Olympus America, Medtronic, Pentax, and GI Supply, and royalites from Elsevier. The other authors disclosed no financial relationships., (Copyright © 2024 American Society for Gastrointestinal Endoscopy. Published by Elsevier Inc. All rights reserved.)

Objective: Symptomatic intracerebral hemorrhage (sICH) after stroke is a devastating neurological complication. Current guidelines support a "possible benefit" of decompressive craniectomy (DC) for large supratentorial sICH with significant mass effect., Methods: The authors conducted a retrospective study of 8 comprehensive stroke centers. They included all patients who sustained an sICH after acute ischemic stroke (AIS), as defined by the Safe Implementation of Thrombolysis in Stroke-Monitoring Study (SITS-MOST), from January 2016 to December 2020. They compared patients who underwent DC to those who were treated with standard medical treatment to measure functional outcome at 90 days, primarily as defined by the modified Rankin Scale (mRS) and secondarily by the Glasgow Outcome Scale-Extended (GOS-E)., Results: Eighty-five patients were identified, 26 of whom (30.5%) underwent DC. Patients who underwent DC were younger (58 years [DC] vs 76 years [no DC], p < 0.001). No patient with a previous history of cancer underwent DC (n = 14, p = 0.004). Twenty-five patients (96.2%) in the DC group underwent thrombectomy versus 54 (91.5%) in the non-DC group (p = 0.443). Patients who underwent DC had a longer ICU stay (median [IQR] 240 [38-408] hours vs 24 [5-96] hours in non-DC patients, p = 0.002). At 90 days, 3 patients (4.1%) had obtained an mRS score of 0-2 and 10 patients (11.7%) an mRS score of 0-3. Patients who had improved functional outcome were younger (mRS score, OR 1.06, 95% CI 1.01-1.10, p = 0.012). Patients with a history of cancer had worse 90-day mRS scores (OR 8.49, 95% CI 1.54-159, p = 0.046). The rate of in-hospital mortality or discharge to hospice was significantly higher in the non-DC cohort (10 [38.5%] patients in the DC cohort vs 38 [64.4%] in the non-DC cohort, p = 0.026). Ninety days later, patients who underwent DC were more likely to have improved outcome (mRS mean rank 30.0 vs 40.0, p = 0.027). In multivariable analysis, history of cancer (OR 12.2, 95% CI 1.26-118, p = 0.031) and older age (OR 1.07, 95% CI 1.02-1.13, p = 0.011) increased the odds of worse mRS outcomes while DC did not (OR 1.34, 95% CI 0.357-5.03, p = 0.665)., Conclusions: DC after sICH did not improve functional outcome at 90 days according to multivariable analysis, although younger age and absence of previous cancer history were associated with improved outcomes.

Intra-alveolar extraction of maxillary third molars always poses a challenge to dental practitioners owing to limited accessibility and minimal space for dental forceps application. Dental elevators facilitate the extraction of such teeth. In the traditional technique as described in the literature, the elevator is always introduced from the mesiobuccal aspect of the tooth to engage the space between the interdental bone and the offending tooth to use it as a fulcrum. However, certain situations prevent proper application of the elevator from the buccal aspect of the offending tooth to bring about luxation. One such situation is a grossly decayed third molar tooth, especially from the mesiobuccal aspect with destruction of the tooth substance extending below the cementoenamel junction. Another such situation is observed in patients presenting with thick and inextensible cheeks but a good interincisal opening. In either situation, it becomes very challenging to achieve a good purchase for luxation of the offending third molar. The authors have therefore described a modified technique of tooth elevation, the palatal elevation technique (PET), using the palatal bone instead of the buccal bone as the fulcrum which was observed to be effective in such situations. In the authors' view, PET is simple and quick and can effectively be employed as an alternative to the traditional technique of tooth elevation in all cases that require an intra-alveolar extraction of maxillary third molars., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Sinai Khandeparker et al.)

Intracranial atherosclerotic disease (ICAD) is a common cause of acute ischemic stroke. ICAD has a high rate of recurrent ischemic stroke despite recommended adequate medical treatment. Endovascular treatment of ICAD has been controversial due to high periprocedural complication in historic randomized clinical trials (RCTs). Recently, a multicenter prospective study of stent placement in patients with high grade intracranial stenosis that evaluated safety and efficacy of Balloon-mounted stents (BMS) in symptomatic ICAD showed low rates of periprocedural stroke (5.6%) than the SAMMPRIS (14.7%) and VISSIT (21.4%) trials. This review highlights the recent evolution of endovascular therapy for symptomatic ICAD.

Objective: To compare our experience with pedicle screw insertion of the thoracolumbar spine utilizing the Cirq robot assistance device compared with traditional paradigm using fluoroscopy., Methods: We prospectively collected data of patients undergoing pedicle screw instrumentation in the thoracolumbar spine performed by a single surgeon at three different centers. One center took delivery of the Cirq robotic assistance device. Remaining two centers used C-arm fluoroscopy. Demographic information, diagnosis, total OR time, intraoperative complications, unexpected return to the operating room, and hospital readmissions within 90 days was compared between the two cohorts., Results: A total of 166 screws were placed during the study period. Forty percent were placed using the Cirq. Two thirds the patients had traumatic diagnoses with remaining degenerative spine disease. There were no misplaced pedicle screws in either group. While total OR time was longer in the Cirq cohort by 123 min (p = 0.04), actual procedural time was not statistically different (p = 0.11). Nonetheless there were also more hospital readmissions in the Cirq cohort compared with the C arm group (p = 0.04)., Conclusions: Thoracolumbar screws inserted using C-arm fluoroscopy utilize less total operating room time with similar accuracy compared with the Cirq robotic assistance device. Further studies are warranted., (© 2022. The Author(s).)

Objective: Middle meningeal artery (MMA) embolization and the Subdural Evacuation Port System (SEPS) are minimally invasive treatment paradigms for chronic subdural hematoma (cSDH). Although SEPS offers acute decompression of local mass effect from a cSDH, MMA embolization has been shown to reduce the rate of cSDH recurrence. In combination, these procedures present a potentially safer strategy to a challenging pathology. The authors present a multi-institutional retrospective case series that assessed the safety, efficacy, and complications of SEPS and MMA embolization for cSDH., Methods: A retrospective review was performed of patients who underwent SEPS placement and MMA embolization for cSDH between 2018 and 2021 at three institutions., Results: One hundred patients with 136 cSDHs and a median age of 73 years underwent both SEPS placement and MMA embolization. Initial Glasgow Coma Scale scores were between 14 and 15 in 81% of patients and between 9 and 13 in 14%. The median initial midline shift (MLS) was 7 mm, with subdural hematoma (SDH) in the left hemisphere (lh) in 30% of patients, right hemisphere (rh) in 34%, and bilateral hemispheres in 36%. Follow-up was available for 86 patients: 93.4% demonstrated decreased MLS, and all patients with lhSDH and rhSDH demonstrated progressive decrease in SDH size. The overall complication rate was 4%, including 1 case of facial palsy and 3 cases of iatrogenic acute SDH. Two subjects (2%) required craniotomy for hematoma evacuation. The rate of good functional outcomes, with modified Rankin Scale (mRS) score < 2, was 89% on final follow-up and the overall mortality rate was 2%. A good mRS score on admission was associated with increased odds of functional improvement at follow-up (p < 0.001)., Conclusions: SEPS placement with MMA embolization for cSDH can be done safely and effectively reduces cSDH size with minimal perioperative morbidity.

Peripheral and tissue-specific alterations in global DNA methylation (5-methylcytosine (5mC)) and DNA hydroxymethylation (5-hydroxymethylcytosine (5hmC)) profiles have been identified as both biomarkers for disease prediction and as hallmarks of dysregulated localized gene networks. Global and gene-specific epigenetic alterations in the 5mC profiles have shown widespread implications in the etiology of polycystic ovary syndrome (PCOS). However, there has been no study in PCOS that integrates the quantification of 5mC and 5hmC signatures alongside the expression levels of DNA methylating and demethylating enzymes as respective indicators of methylation and demethylation pathways. Having previously shown that the 5mC signatures are not substantially altered in PCOS, we assessed the global 5hmC levels in peripheral blood leukocytes and cumulus granulosa cells (CGCs) of 40 controls and 40 women with PCOS. This analysis revealed higher 5hmC levels in CGCs of PCOS women, indicating a more dominant demethylation pathway. Furthermore, we assessed the transcript and protein expression levels of DNA demethylating and methylating enzymes, i.e. ten-eleven translocation methylcytosine dioxygenases (TET1, TET2, TET3) and DNA methyltransferases (DNMT1, DNMT3A and DNMT3B), respectively, in CGCs. The relative transcript and protein expression levels of all three TETs were found to be higher in women with PCOS, and the TET mRNA expression profiles were positively correlated with 5hmC levels in CGCs. Also, all three DNMT genes showed altered transcript expression in PCOS, although only the downregulated DNMT3A transcript was correlated with decreasing 5mC levels. At the protein level, the expression of DNMT1 (maintenance methylation enzyme) was higher, while that of DNMT3A (de novo methylation enzyme) was found to be lower in PCOS compared to controls. Overall, these results indicate that DNA methylation changes in CGCs of PCOS women may arise partly due to intrinsic alterations in the transcriptional regulation of TETs and DNMT3A., (© The Author(s) 2022. Published by Oxford University Press on behalf of European Society of Human Reproduction and Embryology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Remote tele-proctoring has been conducted in neuro-endovascular surgery, however, evidence to support its use in the fellowship training is limited. We demonstrate a novel augmented reality tele-proctoring platform to enable a remote attending to guide a fellow., Methods: A consecutive series of neuro-endovascular cases were performed by a neuro-endovascular fellow with remote guidance from an attending surgeon. The fellow and attending were connected using a commercially available cloud-based platform designed to capture and stream up to four live video feeds from a clinical environment to a remote user. In this setting, two video streams were obtained directly from the anteroposterior and lateral cameras on the biplane. Additional video of the operator from a telescopic camera was streamed live to the remote attending surgeon. The attending could provide immediate vocal feedback and also deploy the platform's augmented reality tools to communicate with the fellow in the angiography suite., Results: A total of 10 cases were performed on eight patients utilizing the cloud-based tele-proctoring platform to facilitate instruction. The series included diagnostic angiograms and interventions such as intracranial balloon angioplasty, carotid stenting, and intracranial stenting. All cases were a technical success. No complications or deaths occurred. When compared to similar cohort of 10 cases prior to these which utilized a traditional instruction paradigm; we saw no differences in contrast use ( p  = 0.38), fluoroscopy time ( p  = 0.85), or technical success., Conclusions: This study demonstrates successful use of an augmented reality tele-proctoring platform to guide a neuro-endovascular fellow through complex neuro-interventional procedures from a remote setting.

Purpose: Alveolar bone grafting is undertaken to provide stability to the dental arch and facilitate the eruption of permanent canine as teeth in the line of cleft usually have an altered pattern of eruption. The purpose of this study was to assess the eruption status and the change in the position and pattern of canine eruption after secondary alveolar bone grafting., Methods: An ambispective cohort study was conducted in patients operated for alveolar bone grafting with unilateral/bilateral alveolar cleft between the age of 9 to 13 years using autogenous iliac crest bone graft. The predictor variables of interest include the preoperative eruption status of canine (completely erupted/partially erupted/unerupted), stage of root development (one-third/two-third/more than two-third/complete) and position (vertical/lateral/buccopalatal) of the canine. The primary outcome variable is the eruption status of the canine (completely erupted/partially erupted/unerupted) at 6 months postoperatively. Secondary outcome variables include the stage of root development, change in the vertical, lateral and buccopalatal position of the canine observed in the first 6 months postoperatively with follow-up at 1 and 3 months. Another secondary outcome variable was the status of bone graft at 6 months postoperatively. Statistical analysis was done using Spearman's rank correlation and ANOVA chi-square test., Result: The study sample consisted of 30 non-syndromic alveolar cleft patients with a mean age of 11.9 years, out of which partial and complete eruption of canine was seen in 43.33 and 36.67%, respectively. The canine was unerupted in 20% of the cases (P = .001). There was evidence of continued root development through the grafted bone. No significant change in the angulation of canine was observed in the postoperative period., Conclusion: Significant change in the eruption status and root development of canine with no statistically significant change in the vertical and lateral angulation during eruption was observed. Identifying these risk factors by continuous postoperative monitoring will help in identifying the malposition at an early stage., (Copyright © 2021 The American Association of Oral and Maxillofacial Surgeons. Published by Elsevier Inc. All rights reserved.)

There is growing evidence of spine injury in abusive head trauma (AHT). Historically, spine injury was considered rare in AHT because of a lack of attributable clinical symptoms or signs and a lack of advanced imaging. Increased use of MRI in AHT has been instrumental in helping identify evidence of ligamentous injuries of the spine. These findings can be difficult to identify on autopsy because of the size and location of the ligaments. Because spinal injury in AHT mostly involves ligamentous and soft tissues and only rarely involves bony fractures, more than 90% of the injury findings are missed on CT or radiography of the spine. Investigation of these findings and the injury patterns should lead to a better understanding of the mechanism of spinal injury. In this pictorial review, we describe the various manifestations of spinal ligamentous injury in AHT, as seen on MRI, in children younger than 48 months.

Studies related to loading ability and delivery of clinically used first-line anti-tuberculosis drugs (ATDs) such as isoniazid, rifampicin, pyrazinamide and streptomycin on the surface of starch-derived bulk and nanopolyurethanes (SBPUs and SNPUs) as drug delivery systems (DDS) have been focused to minimise or remove the drug-associated adverse effects. The efficiencies of nanopolyurethanes obtained from the differently substituted cyclic aliphatic and aromatic isocyanates have been studied for drug loading and release purposes. Different advanced instrumental techniques analysed the structural and morphological properties, thermal stability and crystallinity of the starch nanopolyurethans. Average particle sizes ranging from 27.35-42.38 nm to 126.89-218.60 nm for starch nanopolyurethans, SNPU3i and SNPU4i, respectively, were determined by high-resolution transmission electron microscopy. Similarly, the loading efficiency of ATDs to the surfaces of SNPUs and SBPUs was observed in the range of 60-97% while ATDs-loaded SNPUs showed a sustainable release profile for all ATDs except for streptomycin. However, most SBPUs provided burst-release for all the above-mentioned ATDs in pH-dependent studies. The anti-tuberculosis assay against the Mycobacterium tuberculosis H37Rv strain revealed that streptomycin-loaded SNPU4i and isoniazid-loaded SNPU7i are approximately 42 and 7 times more active than the native streptomycin and isoniazid, respectively.

Background: The intersection of ART and molecular genetic science is fast growing. It is now possible to utilize the advances in molecular genetics for clinical application to detect chromosomal aberrations in preimplanting embryos.As molecular genetic techniques have improved, it is now possible to test the complete characterization of human genome variation with reasonable accuracy. In this article, we have tried to summarize the common current indications of chromosomal analysis of preimplanting embryos in couples having various chromosomal dominant or chromosomal recessive heritable disorders leading to the birth of a new born baby with chromosomal aberrations or leading to repeated miscarriage., Conclusion: The currently available techniques of embryo biopsy have their advantages and shortcomings. Today, preimplantation genetic testing to diagnose a euploid embryo is widely used in clinical practice in couples undergoing IVF ET treatment. By eliminating the transfer of aneuploid embryos, the pregnancy rate improves per embryo transfer and it shortens the time of conception from the start of IVF treatment. We have also discussed the current scenario of the place of PGT-A for routine use in IVF treatment procedure in view of the possible risk of losing euploid embryos due to the shortcoming of the embryo biopsy procedure., Competing Interests: Conflict of interestAuthors have no conflict of interest., (© Federation of Obstetric & Gynecological Societies of India 2020.)

Nanoparticles-based drug delivery is at the forefront in the field of pharmaceutical and medicinal research to eradicate or alleviate the associated impediments, such as prolonged treatment time, high doses, toxicity and resistance problem of anti-tuberculosis drugs for the treatment of age-old tuberculosis disease. Herein, the first-line anti-tuberculosis drugs were loaded into the biodegradable starch nanocrystals and native starch to improve the therapeutic profile addressing the existing issues related to conventional drugs. The loading performance of anti-tuberculosis drugs with starch nanocrystals and native starch was found in the range of 65-95%. According to the release study, the native starch was not appropriate, however, the starch nanocrystals demonstrated sustained release drug delivery for isoniazid and pyrazinamide ranging from 50 to 93% for 24 h; the burst release for streptomycin was reported at pH 2 in 6.5 h while only 14% rifampicin was released at pH 8 buffer. An anti-mycobacterium analysis of strain H37Rv showed that minimum inhibition concentration of starch nanocrystals loaded with isoniazid and pyrazinamide (0.033 μg/mL and 1.25 μg/mL, respectively) were more effective than the parent isoniazid (0.2 μg/mL) and pyrazinamide (25.0 μg/mL) at pH 5.5., (Copyright © 2020. Published by Elsevier Ltd.)

Gram-positive and Gram-negative pathogens exist as planktonic cells only at limited times during their life cycle. In response to environmental signals such as temperature, pH, osmolality, and nutrient availability, pathogenic bacteria can adopt varied cellular fates, which involves the activation of virulence gene programs and/or the induction of a sessile lifestyle to form multicellular surface-attached communities. In Salmonella , SsrB is the response regulator which governs the lifestyle switch from an intracellular virulent state to form dormant biofilms in chronically infected hosts. Using the Salmonella lifestyle switch as a paradigm, we herein compare how other pathogens alter their lifestyles to enable survival, colonization and persistence in response to different environmental cues. It is evident that lifestyle switching often involves transcriptional regulators and their modification as highlighted here. Phenotypic heterogeneity resulting from stochastic cellular processes can also drive lifestyle variation among members of a population, although this subject is not considered in the present review., (Copyright © 2019 Desai and Kenney.)

The adaptive in vivo mechanisms underlying the switch in Salmonella enterica lifestyles from the infectious form to a dormant form remain unknown. We employed Caenorhabditis elegans as a heterologous host to understand the temporal dynamics of Salmonella pathogenesis and to identify its lifestyle form in vivo. We discovered that Salmonella exists as sessile aggregates, or in vivo biofilms, in the persistently infected C. elegans gut. In the absence of in vivo biofilms, Salmonella killed the host more rapidly by actively inhibiting innate immune pathways. Regulatory cross-talk between two major Salmonella pathogenicity islands, SPI-1 and SPI-2, was responsible for biofilm-induced changes in host physiology during persistent infection. Thus, biofilm formation is a survival strategy in long-term infections, as prolonging host survival is beneficial for the parasitic lifestyle., Competing Interests: The authors declare no conflict of interest.

With the rise in nosocomial infections worldwide, research on materials with an intrinsic ability to inhibit biofilm formation has been generating a great deal of interest. In the present work, we describe how thin film material libraries generated by pulsed laser deposition can be used for simultaneously screening several novel metal oxide mixtures that inhibit biofilm formation in a common human pathogen, Salmonella enterica serovar Typhimurium. We discovered that in a material library constructed using two metal oxides, the net effect on biofilm formation can be modeled as an addition of the activities of the individual oxides weighted to their relative composition at that particular point on the library. In contrast, for similar material libraries constructed using three metal oxides, there was a nonlinear relation between the amount of dominant metal oxide and the formation of Salmonella biofilms. This nonlinearity resulted in several useful metal oxide combinations that were not expected from the weighted average predictions. Our novel application will lead to the discovery of additional alternatives for creating antimicrobial surfaces.

Zika virus (ZIKV) has been of major international public health concern following large outbreaks in the Americas occurring in 2015-2016. Most notably, ZIKV has been seen to pose dangers in pregnancy due to its association with congenital abnormalities such as microcephaly. Numerous experimental approaches have been taken to address how the virus can cross the placenta, alter normal fetal development, and disrupt specific cellular functions. Many areas concerning the mechanisms of transmission, especially from mother to fetus, are largely unknown but demand further research. Several promising new studies are presented that provide insight into possible mechanisms of transmission, different cell types affected, and immune responses towards the virus. By aiming to better understand the processes behind altered fetal neuronal development due to ZIKV infection, the hope is to find ways to increase protection of the fetus and prevent congenital abnormalities such as microcephaly. As ZIKV infection is spreading to increasingly more areas and bringing harmful outcomes and birth defects with it, it is imperative to identify the mechanisms of transmitting this infectious agent, consider different genetic backgrounds of hosts and strain types, and navigate methods to protect those affected from the detrimental effects of this newly emerging virus., Competing Interests: None.

Bacteria sense and respond to their environment through the use of two-component regulatory systems. The ability to adapt to a wide range of environmental stresses is directly related to the number of two-component systems an organism possesses. Recent advances in this area have identified numerous variations on the archetype systems that employ a sensor kinase and a response regulator. It is now evident that many orphan regulators that lack cognate kinases do not rely on phosphorylation for activation and new roles for unphosphorylated response regulators have been identified. The significance of recent findings and suggestions for further research are discussed., (© 2016 John Wiley & Sons Ltd.)

Aims: Lateral transtemporal approaches are useful for addressing lesions located ventral to the brainstem, especially when the pathologic diagnosis of the tumor dictates that a gross or near total resection improves outcomes. One approach, the presigmoid approach receives little attention in the pediatric population thus far. We sought to characterize morphometric changes, particularly the clival depth and the petroclival Cobb angle, that occur in the temporal bones of children and draw implications about doing a presigmoid approach in children., Settings and Design: This study was a retrospective study performed at John Sealy Hospital, a level-one trauma center that takes care of pediatric injuries as well., Subjects and Methods: We performed a morphometric analysis of noncontrast computed tomography head studies in 96 boys and 67 girls. Central clival depth and petroclival angle were obtained in the axial plane at the level of the internal auditory meatus using the method described by Abdel Aziz et al., Statistical Analysis Used: Descriptive statistics and Student's t-test to compare groups were calculated using Microsoft Excel., Results: We found no gender difference in mean central clival depth or petroclival angle (P = 0.98 and P = 0.61, respectively). However, when we broke our cohort by age into those younger than 9 years of age and those 10 years or older, we found the petroclival angle decreased by 6.2° which was statistically significant (P < 0.000000006)., Conclusions: These findings suggest that a presigmoid retrolabyrinthine approach is useful for children 9 years of age and younger as the petroclival angle appears to decrease resulting in a shallower clival depression in these patients.

A common strategy by which bacterial pathogens reside in humans is by shifting from a virulent lifestyle, (systemic infection), to a dormant carrier state. Two major serovars of Salmonella enterica, Typhi and Typhimurium, have evolved a two-component regulatory system to exist inside Salmonella-containing vacuoles in the macrophage, as well as to persist as asymptomatic biofilms in the gallbladder. Here we present evidence that SsrB, a transcriptional regulator encoded on the SPI-2 pathogenicity-island, determines the switch between these two lifestyles by controlling ancestral and horizontally-acquired genes. In the acidic macrophage vacuole, the kinase SsrA phosphorylates SsrB, and SsrB~P relieves silencing of virulence genes and activates their transcription. In the absence of SsrA, unphosphorylated SsrB directs transcription of factors required for biofilm formation specifically by activating csgD (agfD), the master biofilm regulator by disrupting the silenced, H-NS-bound promoter. Anti-silencing mechanisms thus control the switch between opposing lifestyles.

Context: Inactivating mutations have been reported in subjects with primary/secondary amenorrhea, whereas activating mutations are rare and seen only in women with ovarian hyperstimulation syndrome (OHSS). In the present study, we describe the functional characterization of the two mutations Val(514)Ala (novel mutation) and Ala(575)Val in FSH receptor (FSHR) identified in women with OHSS developed during in vitro fertilization and primary amenorrhea, respectively., Objective: The objective of the investigation was to study the effect of mutations (514 and 575) on FSHR activity by in vitro functional studies., Setting: The study was conducted at an academic research institute and a private in vitro fertilization clinic., Methods: The site-directed mutagenesis was carried out to generate the mutations at position 514 and 575 in pSG5-FSHR construct. Stable cell lines expressing wild type or each of the mutant receptor were generated using Chinese hamster ovary cells. Functional characteristics of both the mutant receptors were assessed by a radioreceptor assay and a cAMP assay., Results: The mutant receptor 514 showed increased cell surface expression as compared with the wild-type (WT) receptor. Although the hormone binding characteristics were similar to the WT receptor, its signaling activity was distinctly higher at lower dose of FSH as monitored by a cAMP assay. On the other hand, the mutant receptor 575 showed lower cell surface expression and higher internalized hormone receptor complex. Additionally, a dose-dependent increase in the cAMP accumulation was not observed in the case of this mutant as compared with WT., Conclusion: OHSS and primary amenorrhea observed in the two affected women, respectively, could be attributed to the functional characteristics of respective mutant FSHR.

Object: The authors have previously reported on their early experience with sublaminar polyester bands in spine surgery. In this paper, the authors describe the use of sublaminar polyester bands in long-segment posterior instrumented spinal fusions from the upper thoracic spine to the ilium in 21 children and transitional adults with progressive neuromuscular scoliosis. Transitional adults were patients older than 18 years of age with a spinal disorder of pediatric onset, such as spina bifida. This dedicated study represents the first reported use of polyester bands in spine surgery for neuromuscular scoliosis in this patient population in the US., Methods: The authors retrospectively reviewed the demographics and procedural data of patients who underwent posterior instrumented fusion using sublaminar polyester bands for neuromuscular scoliosis., Results: Twenty-one pediatric and adult transitional patients, ranging in age from 10 to 20 years (mean 14 years), underwent posterior instrumented fusion for progressive neuromuscular scoliosis. The average coronal Cobb angle measured 66° before surgery (range 37°-125°). Immediately after surgery, the mean coronal Cobb angle was 40° (range 13°-85°). At last follow-up, the average coronal Cobb angle was maintained at 42° (range 5°-112°). Regarding sagittal parameters, thoracic kyphosis was restored by 8%, and lumbar lordosis improved by 20% after surgery. Mean follow-up duration was 17 months (range 2-54 months). One patient with an aborted procedure due to loss of intraoperative evoked potentials was excluded from the analysis of radiographic outcomes. Mean surgical time was 7 hours 43 minutes (range 3 hours 59 minutes to 10 hours 23 minutes). All patients received either a 12- or 24-mg dose of recombinant human bone morphogenetic protein-2. Average estimated blood loss was 976 ml (range 300-2700 ml). Complications directly related to the use of sublaminar instrumentation included transient proprioceptive deficit (1 patient) and prolonged paraparesis (1 patient). Other complications noted in this series included disengagement of the rod from an iliac screw (1 patient), proximal junctional kyphosis (1 patient), noninfected wound drainage (2 patients), and perioperative death (1 patient). The lessons learned from these complications are discussed., Conclusions: Pedicle screws, laminar/pedicle/transverse process hooks, and sublaminar metal wires have been incorporated into posterior spinal constructs and widely reported and used in the thoracic and lumbar spines and sacrum with varying success. This report demonstrates the satisfactory radiological outcomes of hybrid posterior spinal constructs in pediatric and adult neuromuscular scoliosis that include sublaminar polyester bands that promise the technical ease of passing sublaminar instrumentation with the immediate biomechanical rigidity of pedicle screws and hooks. However, the high neurological complication rate associated with this technique (2/21, or 10%) tempers the acceptable radiographic outcomes.

Takotsubo cardiomyopathy (TC) is a reversible characteristic of left ventricular (LV) ballooning on cardiac imaging without significant coronary artery disease that is precipitated by stress. We performed a retrospective analysis of consecutive patient records to analyze outcomes of patients with TC. Of 100 patients with TC (90% women, mean age 67.7 y, SD = 15.96), 44 patients presented to the emergency room with chest pain, biomarker elevation, and electrocardiographic changes (ST segment elevation in 47%; primary TC) and 56 patients subsequently developed TC after an alternative initial diagnosis (ST segment elevation 27%; secondary TC; P = 0.04). Inciting events differed in those with primary versus secondary TC, with 48% of primary TC patients describing emotional stress; most secondary TC (75%) manifested after a surgical procedure or infection. Average length of hospital stay for primary TC was 6.68 days (SD = 5.32, range 1-28 d) and 18.22 (SD = 20.76, range 3-129 d) for secondary TC (P < .0001). Time to resolution of LV function was equal in both groups. With regard to mortality, eight of nine deaths occurred in secondary TC patients, and all nine deaths were attributable to comorbid medical conditions. Primary TC is frequently related to emotional stress, and carries a benign prognosis. Secondary TC is associated with an acute medical condition and results in a higher death rate.

This study aimed to determine if partial removal of the occipital condyle provides a significant increase in visibility and "angle of attack" for treating lesions with extension ventral to the brainstem in children using CT morphometric data. Morphometric analysis was performed in 199 children using CT scans. Angle of attack was measured for both the paracondylar and transcondylar far lateral approach. Statistical analysis was performed using paired or unpaired Student's t-tests (p<0.05) and linear regression analysis. For the far lateral paracondylar approach, the overall angle of attack was 85 ± 9 degrees (range, 60-119 degrees). The overall angle of attack for the far lateral transcondylar approach was 70 ± 9 degrees (range, 48-105 degrees). This difference was significant (p<0.0001). Based on our data, resection of one-third of the occipital condyle in a far lateral transcondylar approach can improve angle of attack by approximately 15 degrees, regardless of age or sex, in the pediatric age group. It is important to keep in mind that there are risks attendant to resection of the occipital condyle, thus the resection of the occipital condyle in children should not be a mandatory part of the far lateral approach; rather, the decision-making should be individualized and considered on a case-by-case basis., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

During an IVF protocol, exogenous FSH is administered to women for ovulation induction. The ovarian response to gonadotrophin stimulation is variable and unpredictable in these women. The FSHR is the most studied gene in relation to ovarian response. The association of a FSHR gene polymorphism at position 680 (p.Asn680Ser) with ovarian response has been well documented. Recently, a polymorphism at position -29 in the 5'-untranslated region of FSHR (g.-29G>A) has been reported to be associated with poor ovarian response and reduced FSHR expression. The present study evaluated the combined effect of the polymorphisms at positions -29 and 680 of FSHR with type of ovarian response and receptor expression. The two FSHR gene polymorphisms together formed four discrete haplotypes and nine allelic combinations. Various clinical parameters revealed that 75% of the subjects with A/A-Asn/Asn genotype were poor ovarian responders (odds ratio 7.92; P=0.009). The relative FSHR mRNA expression in granulosa cells indicated that subjects with A/A-Asn/Asn genotype express significantly lower level of FSHR as compared to the subjects with G/G-Asn/Ser genotype (P=0.029). These results indicate that A/A-Asn/Asn genotype could be used as a potential marker to predict poor ovarian response. The action of FSH is mediated by its receptor (FSHR) present on the granulosa cells in the ovary. Any alterations in the hormone or its receptor are likely to disrupt its normal function, thus causing infertility. Several alterations (mutations/polymorphisms) of the FSHR gene have been reported in women with primary or secondary amenorrhoea. It has also been reported that FSHR gene polymorphisms are associated with variable ovarian response to FSH stimulation during IVF. Women may show poor or normal or hyperovarian response to FSH stimulation. It is well documented that the level of FSHR expression has a great effect on FSH action and is associated with ovarian response. In the present study, we screened normally menstruating women undergoing IVF due to tubal/male factor or unexplained infertility. We analysed two polymorphisms of FSHR, g-29G>A and p.Asn680Ser, in these women. In the subjects studied, 75% women with A/A-Asn/Asn genotype were observed to be poor ovarian responders to FSH stimulation. FSHR expression at the transcript level was observed to be significantly lower in women with A/A-Asn/Asn genotype as compared to women with G/G-Asn/Ser genotype. We also observed that women with A/A-Ser/Ser genotype were not present in the study population. These findings indicate the significance of A/A-Asn/Asn genotype as a predictive marker for poor ovarian response to FSH stimulation., (Copyright © 2013 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved.)

The development of new therapeutic modalities involves the use of drug carrier, such as liposomes, which can modify pharmacokinetic and bio-distribution of drug profile. Polyene antibiotics incorporation into liposomes improves its availability at the site, bio-distribution and therapeutic index mainly through the engulfment of liposomes by circulating monocytes/macrophages and transportation to the site of infection. Polyene antibiotics (AmB, SJA-95, HA-1-92) and other antibiotics (streptomycin, tobramycin, quinolones, anti-tubercular and anti-cancer drugs), liposomal preparations are described with possible advantages from therapeutic efficacy and toxicity point of view. The polyene macrolide antibiotics liposomal preparations proved to be more effective in the treatment of systemic mycosis. The AmB-cyclodextrin derivatives inclusion complex is a major breakthrough in liposomal preparation which can be converted into aqueous phase of liposome. Liposomal drug incorporated preparation has been one of the important areas of research for developing the existing polyene antibiotics into useful chemotherapeutic agents in clinical medicine. In recent past other antibiotics have also been incorporated into liposomes using wide variety of materials, phosphatidylethanolamine derivatives (pegylated liposomes, enzyme sensitive conjugates, fluidosomes of anti-cancer drugs and poly lactic/glycolic acid microspheres for anti-tuberculosis drugs). In addition, attempts were also made to extend the receptor mediated drug targeting and to review some relevant patents.

Object: Isolated cervical canal stenosis at the level of the atlas (C-1) is a rare cause of cervical myelopathy in the pediatric population. It has been associated with several genetic disorders including spondyloepiphysial dysplasia congenita, Down syndrome, and Klippel-Feil syndrome. The purpose of this study is to highlight the authors' experience with 4 additional pediatric cases, review the literature, and report a new association of this disease with Williams syndrome., Methods: The medical records and radiological imaging studies of 4 patients treated at Texas Children's Hospital for symptomatic hypoplasia of the atlas were retrospectively reviewed. Pertinent patient demographic data, clinical presentation, imaging findings, and outcomes after surgery were recorded. A thorough literature review was performed, allowing the authors to compare and contrast their 4 cases to surgical cases already published in the literature., Results: There were 11 boys and 1 girl in the aggregate series. The average age of the patients was 7 years (range 13 months-14 years), and the duration of symptoms prior to presentation was 6 months (range 0-36 months). The mean sagittal diameter of the spinal canal at the level of the atlas measured from the posterior aspect of the dens to the anterior aspect of the arch of C-1 was 11.9 mm (range 8.3-16 mm) in the aggregate series. In 2 new pediatric patients with hypoplasia of the atlas the disease was associated with Williams syndrome, which has not been previously described. Patients in the aggregate series were followed for an average of 18 months (range 3-50 months). Laminectomy of C-1 provided neurological improvement in all patients who presented., Conclusions: Isolated cervical spinal canal stenosis at the level of the atlas is a rare cause of cervical myelopathy. The authors hope that this report will prompt clinicians to consider it when searching for the origin of signs and symptoms of cervical myelopathy, especially in children.

The authors describe rare cases of congenital hypoplasia of the L-5 pedicles and the congenital absence of the left S-1 pedicle in 2 young girls, respectively, including the presentation, diagnosis, and treatment. Moreover, they review the literature on this clinical entity. The patients presented with intractable chronic low-back pain. Plain radiographs and 2D CT scanning revealed the presence of the aforementioned anomalies. Degenerative changes to adjacent level and contralateral facet joints were thought to be the result of overload and instability and seemed to have led to spondylolisthesis, micromotion at L-5 and S-1, and subsequent low-back pain. The pediatric patients were treated with posterior instrumented fusion with good functional outcomes at a minimum 3-month follow-up. To the best of the authors' knowledge, these are the first reports of intractable low-back pain and spondylolisthesis accompanied by hypoplastic-aplastic pedicles at the lumbosacral junction in children.

Spinal arthrodesis was the first successful treatment for scoliosis, performed by Dr. Russell A. Hibbs in 1911 and later by Dr. Fred H. Albee for tuberculosis. In 1914, Dr. H.P.H. Galloway and Dr. Hibbs began using the method to treat neuromuscular scoliosis in patients with poliomyelitis. However, this treatment approach was plagued by loss of deformity correction over time and high pseudarthrosis rates. The turning point in the operative management of spinal deformities began in 1947 with Dr. Paul Randall Harrington when he started a decade-long process to revolutionize surgical treatment of spinal deformities culminating in the advent of the Harrington Rod, the first successful implantable spinal instrumentation system. During the epoch that he was in practice, Dr. Harrington's achievement influenced the technology and art of spine surgery for his contemporaries and the coming generations of spine surgeons. The purpose of this article is to review the life of Dr. Harrington, and how he has arguably come to be known as "Father of the Modern Treatment of Scoliosis."

Purpose: The authors assess the role of flexible hollow core CO2 laser system (Omniguide system) in resection of intraspinal lipomas., Methods: Eight patients with intraspinal lipomas were operated using an Omniguide laser system over a 22-month period. The age range varied between 6 months and 16 years. All of them had lipoma of the conus medullaris associated with lumbar subcutaneous lipoma. Two of these had previous surgery with resection of the subcutaneous part of the lipoma; in one of them, a partial resection of the conus medullaris lipoma had also been performed. In six, there were no obvious motor or sensory deficits whereas two had gross neurologic deficits, with the deficits occurring in one after the previous decompression. Resection of the conus lipoma, untethering of the spinal cord, and reconstruction of the decompressed conus was performed in all aided with Omniguide laser system. The power settings of the laser system ranged from 4 to 8 W., Results: Subtotal to near-total resection was achieved in all. None of the patients developed any new motor or sensory deficits. Three had postoperative CSF leaks which initially required reoperation with graft resuturing and subsequently placement of lumboperitoneal shunt. One child with preexisting neurologic deficits improved in power over the next 12 months., Conclusion: Flexible CO2 laser system was precise and convenient in decompressing the conus lipomas and untethering of the cord in lumbar spinal lipomas.

Lead sulphide (PbS) quantum dot (QD) sensitized anatase TiO(2) nanocorals (TNC) were synthesized by SILAR and hydrothermal techniques. The TNC, PbS and PbS-TNC samples were characterized by optical absorption, XRD, FT-IR, FESEM and XPS. The results show that PbS QDs are coated on the TNCs, the optical absorption is found to be enhanced and the band edge is shifted to ~693 nm as compared with plain TNCs at 340 nm. The PbS-TNC sample exhibits an improved photoelectrochemical performance with a maximum short circuit current (J(sc)) of 3.84 mA cm(-2). The photocurrent density was found to be enhanced 2 fold, as compared with those of the bare PbS photoelectrode. The total power conversion efficiency of the PbS-TNC electrodes is 1.23%.

New polyene macrolide antibiotic SJA-95 in free as well as liposomal (lip.) forms, with and without interferon-γ (IFN-γ) was studied in mice model of aspergillosis using biological and biochemical parameters viz. colony forming units (CFU) in liver, spleen, kidney, lung and brain, and serum IgG, and interleukin-4 (IL-4). Treatment with free and lip SJA-95 along with IFN-γ prolonged the survival time, reduced CFU in vital organs, decreased serum IgG and IL-4 levels. SJA-95 lip form showed greater antifungal activity as compared to free form. The combined treatment of lip SJA-95 with IFN-γ showed further enhancement in antifungal activity of SJA-95 (lip). The present experimental findings demonstrated IFN-γ might act as a potent modulator in immune reaction during fungal infection and can be a useful adjunctive in antifungal therapy in the management of deep seated systemic mycoses., (Copyright © 2011. Published by Elsevier B.V.)

Cadmium sulfide (CdS) nanoparticle-sensitized titanium oxide nanocorals (TNC) were synthesized using a two-step deposition process. The TiO(2) nanocorals were grown on the conducting glass substrates (FTO) using A hydrothermal process and CdS nanoparticles were loaded on TNC using successive ionic layer adsorption and reaction (SILAR) method. The TiO(2), CdS and TiO(2)-CdS samples were characterized by optical absorption, X-ray diffraction (XRD), FT-Raman, FT-IR, scanning electron microscopy (SEM) and contact angle. Further, their photoelectrochemical (PEC) performance was tested in NaOH, Na(2)S-NaOH-S and Na(2)S electrolytes, respectively. When CdS nanoparticles are coated on TNCs, the optical absorption is found to be enhanced and band edge is red-shifted towards visible region. The TiO(2)-CdS sample exhibits improved photoelectrochemical (PEC) performance with maximum short circuit current of (J(sc)) 1.04 mA cm(-2). After applying these TiO(2)-CdS electrodes in photovoltaic cells, the photocurrent was found to be enhanced by 2.7 and 32.5 times, as compared with those of bare CdS and TiO(2) nanocorals films electrodes respectively. Also, the power conversion efficiency of TiO(2)-CdS electrodes is 0.72%, which is enhanced by about 16 and 29 times for TiO(2), CdS samples., (This journal is © The Royal Society of Chemistry and Owner Societies 2011)

Context: Polymorphisms of the FSHR gene are associated with variable ovarian response to FSH stimulation in subjects undergoing in vitro fertilization (IVF) treatment. The type of ovarian response is correlated with the level of FSH receptor (FSHR) expression on granulosa cells., Objective: We investigated whether the polymorphism at position -29 in the promoter of the FSHR gene may contribute in altered receptor expression., Design and Patients: FSHR polymorphism at position -29 was studied in 100 subjects undergoing IVF treatment. Association of this polymorphism with level of FSHR expression was retrospectively analyzed., Setting: The study was conducted at an academic research institute and private IVF clinic., Methods: The genotype at position -29 of the FSHR gene was studied in IVF subjects by PCR-restriction fragment length polymorphism. Total RNA and protein was extracted from granulosa cells. The relative FSHR mRNA expression was carried out by real-time PCR. The receptor protein expression was evaluated by Western blot and confocal microscopy., Results: The clinical and endocrinological parameters revealed that almost 72% of subjects with the AA genotype at position -29 of FSHR gene were poor ovarian responders (odds ratio 8.63, 95% confidential interval 1.84-45.79; P = 0.001). The lower cleavage intensity predicted by in silico analysis for A allele as compared with the G allele suggest the difference in the DNA-protein binding affinity. The relative expression of FSHR at mRNA and protein level was significantly reduced in subjects with AA genotype as compared with the GG genotype., Conclusion: Poor ovarian response observed in subjects with the AA genotype at position -29 of the FSHR gene is due to reduced receptor expression.

We developed a series of ligand-inducible riboswitches that control gene expression in diverse species of Gram-negative and Gram-positive bacteria, including human pathogens that have few or no previously reported inducible expression systems. We anticipate that these riboswitches will be useful tools for genetic studies in a wide range of bacteria.

Utilization of the aryl-β-glucosides salicin or arbutin in most wild-type strains of E. coli is achieved by a single-step mutational activation of the bgl operon. Shigella sonnei, a branch of the diverse E. coli strain tree, requires two sequential mutational steps for achieving salicin utilization as the bglB gene, encoding the phospho-β-glucosidase B, harbors an inactivating insertion. We show that in a natural isolate of S. sonnei, transcriptional activation of the gene SSO1595, encoding a phospho-β-glucosidase, enables salicin utilization with the permease function being provided by the activated bgl operon. SSO1595 is absent in most commensal strains of E. coli, but is present in extra-intestinal pathogens as bgcA, a component of the bgc operon that enables β-glucoside utilization at low temperature. Salicin utilization in an E. coli bglB laboratory strain also requires a two-step activation process leading to expression of BglF, the PTS-associated permease encoded by the bgl operon and AscB, the phospho-β-glucosidase B encoded by the silent asc operon. BglF function is needed since AscF is unable to transport β-glucosides as it lacks the IIA domain involved in phopho-relay. Activation of the asc operon in the Sal(+) mutant is by a promoter-up mutation and the activated operon is subject to induction. The pathway to achieve salicin utilization is therefore diverse in these two evolutionarily related organisms; however, both show cooperation between two silent genetic systems to achieve a new metabolic capability under selection.

The incidence of systemic fungal infections that has risen dramatically over the past three decades has propelled a continuous need for more potent antifungal drugs. The purpose of this research was to evaluate the chemotherapeutic activity of a new heptaene polyene macrolide antibiotic (SJA-95) and liposomal incorporated SJA-95 (lip. SJA-95) in a mouse model of aspergillosis and cryptococcosis respectively. Lip. SJA-95 was prepared in our laboratory by the proliposome method involving incorporation of the antifungal into the proliposome mixture and its subsequent conversion into a liposomal dispersion by a simple dilution step. Treatment with free SJA-95 and lip. SJA-95, both in aspergillosis and cryptococcosis, progressively prolonged the survival time and decreased the fungal loads in vital organs respectively. A higher LD(50) value of lip. SJA as compared to that of free SJA-95 was indicative of reduced toxicity of lip. SJA-95. Our findings suggest lip. SJA-95 treatment results in prolonged survival time, effective microbiological clearance and reduced toxicity that might help to establish its usefulness as a chemotherapeutic agent in systemic fungal infections with fewer adverse reactions.

Similarities in the phenotype observed in women with FSH receptor mutation and in FSH receptor knockout mice have clearly established a critical role of this protein in normal gonadal function. Two common single nucleotide polymorphisms in the exonic region of the FSH receptor gene have been shown to be associated with altered ovarian response in subjects undergoing gonadotrophin treatment. Recent in-vitro studies have shown that the A allele at the -29 position in the 5 untranslated region of the FSH receptor gene is associated with impaired transcriptional activity. Differential expression of the FSH receptor and its function may be one of the factors responsible for altered ovarian response. These observations prompted a study of the association between FSH receptor genotype at the -29 position and ovarian response in women undergoing gonadotrophin treatment. Analysis of the data revealed that the subjects with AA genotype at the -29 position required the highest amount of exogenous FSH for ovulation induction, and oestradiol concentrations before the day of human chorionic gonadotrophin administration were significantly lower (P = 0.015) compared with the GA genotype. The number of pre-ovulatory follicles and retrieved oocytes were lowest in the subjects with AA genotype. These results indicate that the AA genotype at position -29 may be associated with the poor ovarian response.