Double-blind randomized controlled study showing symptomatic and cognitive superiority of bifrontal over bitemporal electrode placement during electroconvulsive therapy for schizophrenia

BackgroundSeveral studies show that bifrontal electrode placement produces relatively fewer cognitive adverse effects than bitemporal placement during electroconvulsive therapy (ECT) in depression. There are no reports comparing these electrode placements in schizophrenia.ObjectivesThis study compared the clinical and cognitive effects of bifrontal and bitemporal electrode placements in schizophrenia patients referred for electroconvulsive therapy (ECT).Methods122 schizophrenia patients who were prescribed ECT were randomized to receive ECT with either bifrontal (BFECT; n = 62) or bitemporal (BTECT; n = 60) placement. Their concomitant anti-psychotic medications and the number of ECT sessions were not controlled. Psychopathology was assessed using the Brief Psychiatric Rating Scale (BPRS), Bush-Francis Catatonia Rating Scale (BFCRS), and the Nurse Observation Scale for Inpatient Evaluation (NOSIE). Cognitive functions were assessed 24-h after the final ECT using a battery of tests. Clinical improvement was compared using chi-square test, repeated measures ANOVA and analysis of covariance (ANCOVA). Cognitive adverse effects were compared using t-test.ResultsAt the end of 2 weeks (after 6 ECT sessions) 63% and 13.2% of BFECT and BTECT patients respectively had met the response criterion for BPRS (40% reduction in total score; OR = 20.8; 95% CI = 3.61–34.33). BFECT patients showed significantly faster clinical response on BPRS (Time × Group interaction effect: P = 0.001), BFCRS (P < 0.001) and the NOSIE total assets score (P = 0.003). ANCOVA using baseline scores as covariates and treatment-resistance status as between-subject factor showed that BFECT patients had significantly greater improvement in all measures. BFECT patients had significantly higher PGI-memory-scale total score than BTECT patients (t = 5.16; P < 0.001). They also showed superior performance in other cognitive measures.ConclusionsBFECT results in superior clinical and cognitive outcomes than BTECT in schizophrenia patients referred for ECT.     

Lung-enriched Organisms and Aberrant Bacterial and Fungal Respiratory Microbiota after Lung Transplant

Rationale: Long-term survival after lung transplantation is limited by infectious complications and by bronchiolitis obliterans syndrome (BOS), a form of chronic rejection linked in part to microbial triggers. Objectives: To define microbial populations in the respiratory tract of transplant patients comprehensively using unbiased high-density sequencing. Methods: Lung was sampled by bronchoalveolar lavage (BAL) and upper respiratory tract by oropharyngeal wash (OW). Bacterial 16S rDNA and fungal internal transcribed spacer sequencing was used to profile organisms present. Outlier analysis plots defining taxa enriched in lung relative to OW were used to identify bacteria enriched in lung against a background of oropharyngeal carryover. Measurements and Main Results: Lung transplant recipients had higher bacterial burden in BAL than control subjects, frequent appearance of dominant organisms, greater distance between communities in BAL and OW indicating more distinct populations, and decreased respiratory tract microbial richness and diversity. Fungal populations were typically dominated by Candida in both sites or by Aspergillus in BAL but not OW. 16S outlier analysis identified lung-enriched taxa indicating bacteria replicating in the lower respiratory tract. In some cases this confirmed respiratory cultures but in others revealed enrichment by anaerobic organisms or mixed outgrowth of upper respiratory flora and provided quantitative data on relative abundances of bacteria found by culture. Conclusions: Respiratory tract microbial communities in lung transplant recipients differ in structure and composition from healthy subjects. Outlier analysis can identify specific bacteria replicating in lung. These findings provide novel approaches to address the relationship between microbial communities and transplant outcome and aid in assessing lung infections.     

Hybrid hollow silica particles: synthesis and comparison of properties with pristine particles

In the past decade, interest in hollow silica particles has grown tremendously because of their applications in diverse fields such as thermal insulation, drug delivery, battery cathodes, catalysis, and functional coatings. Herein, we demonstrate a strategy to synthesize hybrid hollow silica particles having shells made of either polymer-silica or carbon–silica. Hybrid shells were characterized using electron microscopy. The effect of hybrid shell type on particle properties such as thermal and moisture absorption was also investigated.

Hybrid hollow silica particles, which show different properties compared to their pristine counterparts, have been synthesized.

In the past decade, hollow particles have attracted a great deal of interest because of their unique properties (e.g., high surface area, low density, and encapsulated cavity) compared with their dense counterparts. Hollow particles of several materials, including polymers, silica, titania, carbon, and zinc oxide have been reported.^1–9 Among these, hollow silica particles have attracted great attention from scientists because of their low material cost; well understood chemistry; and potential applications in widespread areas such as thermal insulation, drug delivery, energy storage, phase change encapsulation, catalysis, and superhydrophobic coatings.^10–18 Hollow silica particles can be synthesized using various approaches, such as by employing polymer micelles, immiscible solvent emulsions, inorganic or polymer (e.g., polystyrene) particles, and bacterial or virus cells as templates; by etching solid silica particles; or by spray pyrolysis.^19–25 Polymer micelles or emulsions provide very small particles, but making larger particles and tuning particle size are challenges in this approach. Similarly, the obtained particles typically fuse with one another, and achieving individually separated particles is a challenging task. Inorganic template etching is a time-consuming process, and in many cases, rudiments of inorganic templates remain in the hollow particle cavity if etching is incomplete. Unconventional techniques such as spray drying are inexpensive, but particle size control is difficult. The use of polystyrene particles as templates is attracting much attention because polystyrene particles can be synthesized at low cost with controlled sizes. Polystyrene particle-based synthesis of hollow silica particles involves three steps: (1) synthesis of polystyrene particles, (2) deposition of silica shells on polystyrene particles, and (3) removal of the polystyrene core by burning or dissolving to obtain hollow silica particles.Synthesis of hollow silica particles having shells made of silica alone (pristine hollow particles) is well reported. Some previous efforts have been made to attach surfactant molecules to the surfaces of mesoporous (not hollow) hollow particles. For example, Zhang et al.²⁶ first made porous silica particles by using cetyltrimethylammonium bromide (CTAB) as the template. In the next step, sodium carbonate-based etching was used to create cavities inside the porous particles, thus leading to porous-hollow silica particles. Then, 3-mercaptopropyl-trimethoxysilane (MPTS) was used to attach thiol-group ending surfactants to the surface. Similarly, Ribeiro et al.²⁷ coated solid silica particles with poly(butyl methacrylate) to make superhydrophobic coatings. Similarly, hollow polymer particles have been reported by depositing a polymer layer around solid silica particles, followed by etching the silica core. The same hollow polymer particles were also converted to hollow carbon particles by pyrolysis of polymer.^28,31 However, in this work, shell is made of a single material – polymer or carbon.^28,31 To the best of our knowledge, no work has reported hollow particles with a hybrid shell – shell made of two layers of different materials (inner layer: silica and outer layer: polymer or carbon). Additionally, no previous report has investigated the effect of such an additional layer on the properties of the hollow silica particles. We envisage that such additional layers can change the properties, such as stability against moisture and thermal conductivity, of pristine hollow silica particles.We report the synthesis of hybrid hollow silica particles, characterize these hybrid particles, and compare their properties with the properties of pristine hollow silica particles. Our investigations reveal that by changing the coating material, several intrinsic properties of hollow silica particles can be modified.Hollow silica particles were synthesized by modifying previously reported strategies based on the use of polystyrene particles (synthesis details in ESI S1^†) as a template.¹ For synthesizing hollow silica particles, in a typical experiment, 0.25 g of polystyrene particles were mixed into 100 mL of ethanol/water (ethanol 80 mL, water 20 mL). A suitable amount of tetraethyl orthosilicate was added to make complete shells around the polystyrene particles. To increase the TEOS hydrolysis, 28–30% of ammonium hydroxide was used as a catalyst. Fig. 1a depicts a schematic of hollow particle formation. Fig. 1b shows an SEM image of the polystyrene particles used as templates, and Fig. 1c shows a transmission electron microscope (TEM) image of polystyrene core-silica shell particles. Fig. 1d shows an SEM and Fig. 1e shows a high-angle annular dark-field scanning transmission electron microscopy (HAADF-STEM) image of hollow silica particles obtained after burning the polystyrene core by keeping the sample at 550 °C for 4 h.Open in a separate windowFig. 1(a) Schematic showing synthesis of hollow silica particles. (b) SEM image of polystyrene particles. (c) TEM image of polystyrene core coated with silica shell (core–shell). (d) SEM and (e) HAADF-STEM image of hollow silica particles.There are several polymers that can be used to form coatings on silica.^28–31 Among these, the use of resorcinol is well studied.^28,31 In a typical experiment, 0.25 g of hollow particles (0.25 g) were mixed in water (100 mL). Ammonium hydroxide (28–30%, 500 μL), resorcinol (0.1 g), and formaldehyde (150 μL) were added to this reaction mixture. The reaction was allowed to proceed overnight (≈16 h) to completion. Expected mechanism for polymer coating formation is explained in ESI S3.^†Fig. 2a shows a schematic of the process used to make a polymer (polyresorcinol) coating on a silica shell. Fig. 2b shows low-magnification (i) and high-magnification (ii) TEM images of polymer-coated hollow silica particles. The polymer coating can be clearly seen (light in contrast) around the silica shell (dense in contrast). Though TEM imaging confirmed the presence of a polymer coating on the surface of the silica, to further confirm the formation of the coating, we applied electron energy loss spectroscopy (EELS). Energy dispersive X-ray (EDX) imaging is easy to use and is a readily available technique for analysing materials; however, EDX has a very low sensitivity to low-atomic-weight elements such as carbon and oxygen. Therefore, it was not a suitable technique for confirming the polymer presence. In contrast, EELS is known for its high sensitivity to low-atomic-weight elements (e.g., carbon and oxygen). Fig. 2c shows scanning HAADF-STEM (i) and EELS (ii) images of the polymer-silica hybrid shell. The coating was quite uniform, with some thicker areas on the free surfaces of particles and some thinner areas at the joints in aggregated particles (ESI S2^†). Therefore, if individual uniform coatings are required, the original hollow particle samples must be properly disaggregated.Open in a separate windowFig. 2(a) Schematic showing the polymer coating process. (b) TEM images of polymer-coated silica particles. (c) HAADF-TEM (i) and EELS S map (ii) showing polymer and silica layers of hybrid shell.Additionally, we demonstrated the formation of hybrid hollow silica particles with outer layers made of carbon and inner layers made of silica. To form a carbon layer on a silica shell, the initial polymer coating was sintered in an inert atmosphere (argon) at 550 °C for 4 h. Fig. 3a shows a schematic of polymer layer conversion to a carbon layer. Under these conditions, polymer converts into carbon instead of being completely oxidized into carbon dioxide and water. After heating under an inert atmosphere, brown polymer-coated particles changed to black carbon-coated particles. Separate carbon (outer) and silica (inner) layers were observed in TEM (Fig. 3b) and EELS images (Fig. 3c).Open in a separate windowFig. 3(a) Schematic showing conversion of polymer coating to carbon coating. (b) TEM images of carbon-coated particles. (c) EELS element map showing the carbon layer on a silica shell.In addition to making hybrid shell hollow particles, we investigated whether the coating affected the properties (e.g., thermal conductivity and moisture absorption) of the pristine hollow silica particles. We measured the thermal conductivity of pristine, polymer-coated, and carbon-coated particles. The results showed that polymer-coated particles had the lowest thermal conductivity and carbon-coated particles had the highest thermal conductivity of the three types. The Fig. 4 plot shows the thermal conductivities of the three types of particles, and respective insets show photos of corresponding particle samples. More details of the measurements are provided in ESI-S3.^† As expected, the polymer silica particles had lower thermal conductivity (0.022 ± 0.002 W m⁻¹ K⁻¹) than pristine hollow particles (0.024 ± 0.002 W m⁻¹ K⁻¹), whereas carbon-coated particles had higher thermal conductivity (0.036 ± 0.004 W m⁻¹ K⁻¹) than both the pristine and the polymer-coated particles. This information provides a new tool to achieve or tune thermal properties of hollow silica particles as desired. For example, for high-thermal-insulation materials, polymer-coated particles are ideal; whereas carbon-coated particles are more suitable where somewhat higher thermal conductivity, but hydrophobicity is required. We were expecting that a carbon coating will increase electrical conductivity of hollow particles, however, we observed that even carbon coated particles had an electrical resistance in the megaOhm range, i.e., behave as electrically insulators (measurement details in ESI S3^†). Although the thermal conductivity of polymer-coated or carbon-coated hollow silica particles can be further modified by modifying the coating thickness, in the present work, we did not investigate the effect of coating thickness on thermal conductivity in detail. We expect the thinner the coating, the lower the thermal conductivity will be. We observed in both the polymer- and carbon-coated particles that the coatings were not uniform. Some particles had thick and others thin coatings, indicating that coating nucleation was not uniform, and the coatings may have begun forming earlier on some particles than on others. We observed that carbon–silica hollow particles are hydrophobic in nature, staying afloat on water for several hours (ESI Fig. S4^†) and mixing in water only after vigorous stirring. It appears that, with stirring, water molecules enter the hollow particle cavities through the pores present in the carbon and silica shells and wet the inner parts of the cavities, thus causing the particles to mix in water.Open in a separate windowFig. 4Effect of different types of coatings on the thermal conductivity of hollow silica particles. Insets show the photos of respective particles.Additionally, we compared the moisture absorption properties of pristine hollow silica particles with those of polymer- and carbon-coated hollow silica particles (Fig. 5). Moisture absorption/desorption experiments were performed using a dual vapor gravimetric sorption analyser. We observed that polymer-coated particles absorbed less humidity compared with pristine particles at the same relative humidity. However, both materials had similar isotherm profiles in which the moisture adsorption capacity increased at relatively higher moisture concentrations. The carbon-coated particles, on the other hand, showed a completely different isotherm behaviour: an immediate increase in adsorption capacity was observed between 30% and 50% relative humidity. A sharp increase in moisture absorption at higher relative humidity (between 30–50%) appears due to the entry of water vapors inside the particles because of porous nature of carbon layer. Similar shape of isotherms for pristine and polymer coated particles indicates that both of these particles had similar surface groups (–OH), but lower absorption in polymer coated particles compared to pristine particles indicates that its surface has a small number of moisture absorbing groups (–OH) compared to pristine particles. The hysteresis between adsorption and desorption isotherms was found to be minimal, indicating that the samples had similar performance for adsorption or desorption process. We expect this information to be helpful for applications such as developing water-stable coatings or insulation materials by using hollow silica particles.Open in a separate windowFig. 5Effect on moisture adsorption and desorption process. Plot showing behaviour of hollow particles under different relative humidity conditions for pristine and coated samples.     

Association of rs11643718 SLC12A3 and rs741301 ELMO1 Variants with Diabetic Nephropathy in South Indian Population

This study reports on the association of genetic variants selected from previous genome‐wide association studies for type 2 diabetic nephropathy in south Indians. Eight variants were genotyped in 601 type 2 diabetic subjects without nephropathy (DM) and 583 type 2 diabetic subjects with nephropathy (DN) by MassARRAY. The minor allele frequencies of rs11643718 SLC12A3 variant and rs741301 ELMO1 variant were significantly different between DM and DN groups (P = 0.029 and 0.016, respectively). A combined analysis showed that the subjects carrying the risk genotypes of both these variants (GG of rs11643718 + AG/AA of rs741301) had a significant association with DN with an odds ratio [adjusted for age, sex, Body Mass Index (BMI), HbA1c, and systolic Blood Pressure (BP)] of 1.73 (1.30–2.30, P = 1.72 × 10^–4) as compared to subjects carrying all other genotype combinations. This is the first study to report a significant association of the SLC12A3 rs11643718 and ELMO1 rs741301 (Single nucleotide Polymorphism) SNPs with diabetic nephropathy in south Indians.     

Microsurgical clipping versus newer endovascular techniques in treatment of unruptured anterior communicating artery-complex aneurysms: a meta-analysis and systematic review

The aim of this study is to compare occlusion rate, complication rate, and clinical outcome of microsurgical clipping (MC) and advanced endovascular techniques (EVT) in unruptured anterior communicating artery-complex aneurysms (ACoCAs). We reviewed the scientific literature reporting occlusion rate, time of occlusion assessment, and clinical outcome of MC and EVT in patients with unruptured ACoCAs, from January 2009 to December 2019. We included in our analysis 25 studies and 872 patients with unruptured ACoCAs (434 treated with endovascular techniques and 438 with MC). Ninety-three (10.7%), 320 (36.7%), 21 (2.4%), and 438 (50.2%) were treated with flow diverter (FD), stent-assisted coiling (SAC), endosaccular devices (ES), and microsurgical clipping (MC) respectively. FD, SAC, ES, and MC subgroups presented minor complications in 11.8%, 3.8%, 14.3%, and 7.1% of cases (p=.016), and major complications in 3.2%, 4.4%, 0%, and 7.1% (p=.136) of patients. A total occlusion rate post-treatment has been achieved in 4.3%, 87.1%, 47.6%, and 98.2% of cases (p=.000), while at 12 months’ follow-up in 50%, 66%, 83.3%, and 80% of patients (p=.001). FD, SAC, ES, and MC subgroups had a good clinical outcome at 12 months in 93.5%, 90.5%, 100%, and 67.8% of cases. MC is associated with higher post-treatment total occlusion rate, but higher complication and lower good clinical outcome rates. EVT are promising in treating unruptured anterior cerebral artery aneurysms with high margin of safety and good clinical outcome, despite the lower total occlusion rate.

     

Sevoflurane for trans-sternal thymectomy in myasthenia gravis

Myasthenic gravis (MG) is an autoimmune disease associated with acetylcholine receptor deficiency. Patients with MG exhibit increased sensitivity to non-depolarising muscle relaxants. In an attempt to avoid neuromuscular blockers, we used sevoflurane in two myasthenic patients undergoing trans-sternal thymectomy. Inhalation of 8% sevoflurane in oxygen using vital capacity technique produced rapid, pleasant and smooth induction and provided good tracheal intubating conditions. In both patients anaesthesia was maintained with 1.5-2% end-tidal concentration of sevoflurane and nitrous oxide in oxygen without adjunctive neuromuscular blocking agents. There were minimal changes in cardiovascular variables and recovery was faster. It is suggested that sevoflurane may be the main anaesthetic for both induction and maintenance in myasthenic patients undergoing trans-sternal thymectomy.     

Asplenia syndrome in a child with a balanced reciprocal translocation of chromosomes 11 and 20 [46,XX,t(11;20)(q13.1;q13.13)]

We present a 6-year-old girl with a balanced 11;20 translocation [46,XX,t(11;20)(q13.1;q13.13)pat], asplenia, pulmonic stenosis, Hirschsprung disease, minor anomalies, and mental retardation. This case represents the second report of an individual with situs abnormalities and a balanced chromosome rearrangement involving a breakpoint at 11q13. Polymerase chain reaction (PCR) analysis of microsatellite markers excluded uniparental disomy for chromosomes 11 and 20. Segregation analysis of markers in the 11q13 region in the proposita and her phenotypically normal carrier sibs did not show a unique combination of maternal and paternal alleles in the patient. We discuss several possible explanations for the simultaneous occurrence of situs abnormalities and a balanced 11;20 translocation. These include (1) chance, (2) a further chromosome rearrangement in the patient, (3) gene disruption and random situs determination, and (4) gene disruption plus transmission of a recessive or imprinted allele from the mother. © 1996 Wiley-Liss, Inc.