The safety of CAR-T cells and PD-1 antibody combination on an experimental model.

Chimeric antigen receptor (CAR) T cells and PD-1 antibodies (PD-1 Ab) are emergent immunotherapies with unprecedented efficacy. The presence of PD-1 on T cells contributes to hypofunction of CAR-T therapy and inhibition of PD-1 enhances anti-cancer effect of CAR-T cells. Therefore, the combination of CAR-T cells and PD-1 antibody is a promissing strategy for cancer treatment. This study aims to establish our in-house CAR-T cells and evaluate the safety of CAR-T cells in combination with PD-1 antibody in animals. The toxicity of CD19-CAR-T cells was examined using Swiss Webster mice. Four mouse groups were treated with control, CAR-T, PD-1 antibody or CAR-T + PD-1 antibody. Mice's overall status was monitored and recorded. At the end-point, hematological and biochemical indices were quantified, histopathology of liver and kidney was evaluated by pathologists. The relative abnormal ratio and absolute values were compared between groups. We generated our in-house CAR-T cells and used them for safety evaluation in mice. The increase in mouse weight was observed in all groups after treatment and the weight was comparable between groups. The hematological, biochemical and histopathological parameters were equivalent between groups, except for liver grain degeneration occurred in treatment groups. Thus, CAR-T cells, PD-1 Ab and their combination were safe in mice. We successfully produced our in-house CAR-T cells and the combination of our CAR-T cells and PD-1 antibody was safe in mice with comparable values of hematopoietic indices, liver and kidney functions. Longer follow-up might be necessary to evaluate their effect on the liver.

Mechanistic understanding of N2 activation: a comparison of unsupported and supported Ru catalysts.

N2 dissociative adsorption is commonly the rate-determining step in thermal ammonia synthesis. Herein, we performed density functional theory (DFT) calculations to understand the N2 dissociation mechanism on models of unsupported Ru(0001) terraces, Ru B5 sites, and polar MgO(111)-supported Ru8 cluster mimicking a B5 site geometry, denoted (Ru8(B5-like)/MgO(111)). The activation energy of N2 dissociative adsorption on the Ru8(B5-like)/MgO(111) model (Ea = 0.33 eV) is much lower than that on the unsupported Ru(0001) terrace (Ea = 1.74 eV) and Ru B5 (Ea = 0.62 eV) models. The lower N2 dissociation barrier on Ru B5 sites is facilitated by the enhanced σ donation and π* back-donation between N2(σ, π*) and Ru(d) orbitals resulting in the stronger activation of the molecular side-on N2* dissociation precursor. The Ru8(B5-like)/MgO(111) also exhibits enhanced σ donation because of the B5-like cluster geometry. Furthermore, the Ru cluster of the bare Ru8(B5-like)/MgO(111) model is positively charged. This induced an unusual π donation from N2(π) to Ru(d) orbitals as revealed by analyses of the density of states and partial charge densities. The combined σ and π donation resulted in an increased synergistic π* back-donation. The total interactions between N2(σ, π, π*) and Ru(d) resulted in an overall electron transfer to the adsorbed N2 from the Ru atoms in the B5-like site with no direct involvement of the MgO(111) substrate. Analyses of bond stretching vibrations and bond lengths show that the N2(σ, π, π*) and Ru(d) interactions lead to a weaker N-N bond and stronger Ru-N bonds. These correspond to a lower barrier of N2 dissociation on the Ru8(B5-like)/MgO(111) model, where the highest red-shift of N-N vibration and the longest N-N bond length were observed after side-on N2* adsorption. These results demonstrate that an electron-deficient Ru catalyst are not always inhibited from donating electrons to adsorbed N2. Rather, this study shows that the electron deficiency of Ru can promote π* back-donation and N2 activation. These new insights may therefore open new avenues to design supported Ru catalysts for nitrogen activation.

Auxeticity of monolayer, few-layer, vdW heterostructure and ribbon penta-graphene.

Using molecular statics simulations, we specifically focus on investigating the negative Poisson's ratio of the monolayer, few-layer, van der Waals, and ribbon penta-graphene. As a result, we provide evidence to show that the Poisson's ratio is the combination of bond stretching and angle rotating mechanism. The auxeticity of monolayer penta-graphene is due to the dominance of bond stretching. However, the significant effect of the angle rotating mechanism causes the enhancement of the in-plane Poisson's ratio of few-layer penta-graphene. Furthermore, the elongation of interlayer bonds results in a negative out-of-plane Poisson's ratio in few-layer penta-graphene. The strong dependence of Poisson's ratio on stacking configuration and number of layers was found. We also show that the van der Waals interaction slightly enhances the auxeticity of heterostructure penta-graphene. Finally, we discuss the significant effects of warped edges on the auxeticity of penta-graphene ribbons.

Cluster Nanozymes with Optimized Reactivity and Utilization of Active Sites for Effective Peroxidase (and Oxidase) Mimicking.

Single-atom catalysts have attracted attention in the past decade since they maximize the utilization of active sites and facilitate the understanding of product distribution in some catalytic reactions. Recently, this idea has been extended to single-atom nanozymes (SAzymes) for the mimicking of natural enzymes such as horseradish peroxidase (HRP) often used in bioanalytical applications. Herein, it is demonstrated that those SAzymes without constructing the reaction pocket of HRP still undergo the OH radical-mediated pathway like most of the reported nanozymes. Their positively charged single-atom centers resulting from support electronegative oxygen/nitrogen hinder the reductive conversion of H2 O2 to OH radicals and hence display low activity per site. In contrast, it is found that this step can be facilitated over their metallic counterparts on cluster nanozymes with much higher site activity and atom efficiency (cf. SAzymes with 100% atom utilization). Besides the mimicking of HRP in glucose detection, cluster nanozymes are also demonstrated as a better oxidase mimetic for glutathione detection.

Negative out-of-plane Poisson's ratio of bilayer graphane.

With its excellent mechanical and thermal properties, bilayer graphane is a promising material for realizing future nanoelectromechanical systems. In this study, we focus on the auxetic behavior of bilayer graphane under external loading along various directions through atomistic simulations. We numerically and theoretically reveal the mechanism of the auxeticity in terms of intrinsic interactions between carbon atoms by constructing bilayer graphane. Given that the origin of the auxeticity is intrinsic rather than extrinsic, the work provides a novel technique to control the dimensions of nanoscale bilayer graphane by simply changing the external conditions without the requirement of complex structural design of the material.

Urinary neutrophil gelatinase-associated lipocalin predicted to contrast-associated acute kidney injury after planned percutaneous coronary intervention in elderly patients.

AIM: To determine the proportion of contrast-associated acute kidney injury (CA-AKI) after percutaneous coronary intervention (PCI) and the predictive value of urine neutrophil gelatinase-associated lipocalin (uNGAL) for CA-AKI in elderly patients with chronic coronary artery disease. METHODS: A total of 509 patients who had planned percutaneous coronary intervention (mean age was 63.58 ± 11.63 years and 63.3% of males) were divided into two groups: group 1 (n = 153; elderly patients) with ≥70 years old and group 2 (n = 356) with <70 years old. Urine NGAL was measured by the ELISA method. Clinical and laboratory data were collected on the day before intervention. CA-AKI was defined based on Kidney Disease: Improving Global Outcomes criteria. RESULTS: The ratio of CA-AKI in group 1 was 23.5% which was higher than that of group 2 (8.7%) with a p-value < 0.001. Urine NGAL level in group 1 was significantly higher than that of group 2 [31.3 (19.16-55.13) ng/ml vs. 19.86 (13.21-29.04) ng/ml, p < 0.001]. At a cut-off value of 44.43 ng/ml, uNGAL had a predictive value for CA-AKI in all patients (AUC = 0.977, p < 0.001). Especially at a cut-off value of 44.14 ng/ml, uNGAL had a predictive value for CA-AKI in elderly patients (AUC = 0.979, p < 0.001). CONCLUSIONS: The rate of CA-AKI after PCI in elderly patients was 23.5%. Urine NGAL before PCI had a good predictive value for CA-AKI in elderly patients with chronic coronary artery disease.

Combined Gap-Polymerase Chain Reaction and Targeted Next-Generation Sequencing Improve α- and ß-Thalassemia Carrier Screening in Pregnant Women in Vietnam.

Vietnam has a high thalassemia burden. We collected blood samples from 5880 pregnant Vietnamese women during prenatal health checks to assess thalassemia carrier frequency using combined gap-polymerase chain reaction (gap-PCR) and targeted next-generation sequencing (NGS). Thalassemia carriers were identified with prevalence of 13.13% (772), including 7.82% (460) carriers of α-thalassemia (α-thal), 5.31% (312) carriers of ß-thalassemia (ß-thal), and 0.63% (37) concurrent α-/ß-thal carriers. Deletional mutations (368) accounted for 80.0% of α-thal carriers, of which, --SEA (Southeast Asian) (n = 254; 55.0%) was most prevalent, followed by the -α3.7 (rightward) (n = 66; 14.0%) and -α4.2 (leftward) (n = 45; 9.8%) deletions. Hb Westmead (HBA2: c.369C>G) (n = 53) and Hb Constant Spring (Hb CS or HBA2: c.427T>C) (in 28) are the two most common nondeletional α-globin variants, accounting for 11.5 and 6.0% of α-thal carriers. We detected 11 different ß-thal genotypes. Hb E (HBB: c.79G>A) (in 211) accounted for 67.6% of ß-thal carriers. The most common ß-thal genotypes were associated with mutations at codon 17 (A>T) (HBB: c.52A>T), codons 41/42 (-TTCT) (HBB: c.126_129delCTTT), and codon 71/72 (+A) (HBB: c.217_218insA) (prevalence 0.70%, 0.68%, and 0.2%, respectively). Based on mutation frequencies calculated in this study, estimates of 5021 babies in Vietnam are affected with clinically severe thalassemia annually. Our data suggest a higher thalassemia carrier frequency in Vietnam than previously reported. We established that combining NGS with gap-PCR creates an effective large-scale thalassemia screening method that can detect a broad range of mutations.

Orthodontic Management of a Palatal Fistula in a Patient With Pierre Robin Sequence Using 3D Intraoral Scanning and Computer-Aided Design.

Pierre Robin sequence (PRS) is a rare congenital abnormality that may be classified as a first branchial arch syndrome. Patients with PRS who present with cleft palate have a deformity to the soft or hard palate of the maxilla that is repaired within the first year of birth. Despite the repair, patients may experience oronasal complications. Surgical repair is usually necessary if palatal fistula presents, and prosthetic obturators are used to provide temporary relief prior to surgery. This case report outlines the steps in the successful fabrication of a custom-fitted temporary vacuum-formed prosthetic obturator using computer-aided design technology to provide a more comfortable and effective treatment option for the patient.

Structural evolution of atomically dispersed Pt catalysts dictates reactivity.

The use of oxide-supported isolated Pt-group metal atoms as catalytic active sites is of interest due to their unique reactivity and efficient metal utilization. However, relationships between the structure of these active sites, their dynamic response to environments and catalytic functionality have proved difficult to experimentally establish. Here, sinter-resistant catalysts where Pt was deposited uniformly as isolated atoms in well-defined locations on anatase TiO2 nanoparticle supports were used to develop such relationships. Through a combination of in situ atomic-resolution microscopy- and spectroscopy-based characterization supported by first-principles calculations it was demonstrated that isolated Pt species can adopt a range of local coordination environments and oxidation states, which evolve in response to varied environmental conditions. The variation in local coordination showed a strong influence on the chemical reactivity and could be exploited to control the catalytic performance.

Chitinophaga vietnamensis sp. nov., a multi-drug resistant bacterium infecting humans.

We describe a new multidrug resistant Chitinophaga species that was isolated from patients with type 2 diabetes in Vietnam. Strain BD 01T was cultivated in 2017 from a blood sample of a patient suffering from bacteremia. Strain VP 7442 was isolated in 2018 from a pleural fluid sample of a patient who had presented with lung abscess and pleural effusion. Both strains are aerobic, Gram-negative, non-motile and non-spore-forming. The 16S rRNA gene sequences of both strains are 100 % similar and share a highest 16S sequence identity with Chitinophaga polysaccharea MRP-15T of 97.42 %. Their predominant fatty acid is iso-C15 : 0 (73.8 % for strain BD 01T and 79.8 % for strain VP 7442). The draft genome sizes of strains BD 01T and VP 7442 are 6 308 408 and 6 308 579 bp, respectively. They are resistant to beta-lactams, aminoglycosides, fluoroquinolones, metronidazole, fosfomycin, vancomycin and macrolides, and exhibit 20 and 18 antimicrobial resistance-related genes, respectively. Using the multiphasic taxonogenomic approach, we propose that strains BD 01T (=CSUR P9622=VTCC 70981) and VP 7442 (=CSUR P9623=VTCC 70982) represent a new species, for which we propose the name Chitinophaga vietnamensis sp. nov. Strain BD 01T was chosen as type strain of C. vietnamensis sp. nov.

Assessing antimicrobial misuse in small-scale chicken farms in Vietnam from an observational study.

BACKGROUND: Antimicrobials are used by poultry farmers in Vietnam as a tool to treat and prevent infectious diseases. We aimed to determine the fraction of disease episodes likely to remain untreated due to the administration of antimicrobials on non-susceptible pathogens in chicken flocks in the Mekong Delta of Vietnam. Weekly data on antimicrobial use and clinical signs were collected from 88 randomly chosen chicken flocks over 124 full production cycles (i.e. time between restocking flocks with day-old chicks and sale for slaughter). A naïve Bayes model was trained to infer the probabilities of disease episodes having been caused by each of 24 pathogens, given the observed clinical sign profile, and expert knowledge on their relative incidence. RESULTS: A total of 224 disease episodes were observed, of which 44.8% were attributed to viruses (95% CI 31.1-58.4%), 54.6% (CI 40.4-68.7%) to bacteria, and 0.6% (CI 0-1.7%) to a protozoan (Eimeria spp.). Antimicrobials were more frequently administered on weeks with disease than on weeks without disease (43.3% vs. 17.8%; p < 0.001). A median of 2 [IQR 0-4] antimicrobials were used by episode. The choice of specific antimicrobials was independent on whether the flocks had disease clinical signs or not. Antimicrobials were not used in 30.3% of the episodes. The overall probability that episodes were not effectively treated was 74.2, and 53.7% when discounting cases where the inferred aetiology is viral. Considering only episodes where antimicrobials were given, these probabilities were 57.4 and 23.8% respectively. CONCLUSIONS: This study highlights untargeted use of antimicrobials on small-scale Vietnamese chicken farms, as well as the limitations of antimicrobials as effective tools to control infectious diseases.

Chemical composition, Aedes mosquito larvicidal activity, and repellent activity against Triatoma rubrofasciata of Severinia monophylla leaf essential oil.

Aedes aegypti and Ae. albopictus are key vectors in the spread of arboviruses such as dengue, chikungunya, yellow fever, and Zika. Triatoma rubrofasciata is an "assassin bug" whose populations and association with humans have dramatically increased and may represent a serious health concern. Control of insect vectors is a logical course of action to prevent the spread of these insect-borne infections. This work presents the leaf essential oil composition, mosquito larvicidal activities, and insect-repellent activity of Severinia monophylla. The essential oil of S. monophylla from Vietnam was obtained by hydrodistillation and analyzed by gas chromatography and mass spectrometry. The major components were sabinene, ß-caryophyllene, bicyclogermacrene, germacrene D, (E)-nerolidol, globulol, and linalool. The leaf essential oil showed remarkable larvicidal activity against Ae. aegypti with LC50 (48 h) of 7.1 µg/mL and Ae. albopictus with LC50 (48 h) of 36 µg/mL. The essential oil also showed repellent activity on T. rubrofasciata at a concentration of 0.5%.

Transcriptome profiling of short-term response to chilling stress in tolerant and sensitive Oryza sativa ssp. Japonica seedlings.

Low temperature is a major factor limiting rice growth and yield, and seedling is one of the developmental stages at which sensitivity to chilling stress is higher. Tolerance to chilling is a complex quantitative trait, so one of the most effective approaches to identify genes and pathways involved is to compare the stress-induced expression changes between tolerant and sensitive genotypes. Phenotypic responses to chilling of 13 Japonica cultivars were evaluated, and Thaibonnet and Volano were selected as sensitive and tolerant genotypes, respectively. To thoroughly profile the short-term response of the two cultivars to chilling, RNA-Seq was performed on Thaibonnet and Volano seedlings after 0 (not stressed), 2, and 10 h at 10 °C. Differential expression analysis revealed that the ICE-DREB1/CBF pathway plays a primary role in chilling tolerance, mainly due to some important transcription factors involved (some of which had never been reported before). Moreover, the expression trends of some genes that were radically different between Thaibonnet and Volano (i.e., calcium-dependent protein kinases OsCDPK21 and OsCDPK23, cytochrome P450 monooxygenase CYP76M8, etc.) suggest their involvement in low temperature tolerance too. Density of differentially expressed genes along rice genome was determined and linked to the position of known QTLs: remarkable co-locations were reported, delivering an overview of genomic regions determinant for low temperature response at seedling stage. Our study contributes to a better understanding of the molecular mechanisms underlying rice response to chilling and provides a solid background for development of low temperature-tolerant germplasm.

Electronic structure of Al, Ga, In and Cu doped ZnO/Cu(111) bilayer films.

The effect of doping with group-III metals (Al, Ga and In) and Cu free standing and Cu(111) supported ZnO bilayer films has been investigated computationally by using the DFT+U method including dispersion contributions. The changes in the electronic properties of doped ZnO and ZnO/Cu(111) films have been tested by adsorbing CO probe molecules. The replacement of a lattice Zn ion in a free-standing ZnO bilayer by a group-III element generates an extra electron whose distribution depends on the dopant. In particular, while the excess electron is delocalized over the conduction band for Al or Ga doping, it is localized on the dopant in the case of In. The situation is different on the supported ZnO/Cu(111) film, where the extra electron is transferred to the underlying Cu support. While the CO adsorption energy at the doped sites in the ZnO bilayer is the same as in the ZnO/Cu(111) ultrathin films, CO exhibits a larger red-shift in the unsupported ZnO bilayer. The oxidation state of Cu replacing Zn in the unsupported ZnO films is 2+, Cu(3d9) state, while it is 1+, Cu(3d10) state, in the ZnO/Cu(111) supported films where a charge transfer from the supporting Cu metal to the Cu impurity occurs. Cu doping results in a stronger interaction with CO and a large red-shift of the CO stretching frequency. In this respect, Cu doping of ZnO/Cu(111) bilayer films could have interesting consequences in gas adsorption while doping with group-III elements does not lead to major changes of the adsorption properties when the free-standing ZnO films are compared to the supported ZnO/Cu(111) counterparts.

Development and evaluation of a non-ribosomal random PCR and next-generation sequencing based assay for detection and sequencing of hand, foot and mouth disease pathogens.

BACKGROUND: Hand, foot and mouth disease (HFMD) has become a major public health problem across the Asia-Pacific region, and is commonly caused by enterovirus A71 (EV-A71) and coxsackievirus A6 (CV-A6), CV-A10 and CV-A16. Generating pathogen whole-genome sequences is essential for understanding their evolutionary biology. The frequent replacements among EV serotypes and a limited numbers of available whole-genome sequences hinder the development of overlapping PCRs for whole-genome sequencing. We developed and evaluated a non-ribosomal random PCR (rPCR) and next-generation sequencing based assay for sequence-independent whole-genome amplification and sequencing of HFMD pathogens. A total of 16 EV-A71/CV-A6/CV-A10/CV-A16 PCR positive rectal/throat swabs (Cp values: 20.9-33.3) were used for assay evaluation. RESULTS: Our assay evidently outperformed the conventional rPCR in terms of the total number of EV-A71 reads and the percentage of EV-A71 reads: 2.6 % (1275/50,000 reads) vs. 0.1 % (31/50,000) and 6 % (3008/50,000) vs. 0.9 % (433/50,000) for two samples with Cp values of 30 and 26, respectively. Additionally the assay could generate genome sequences with the percentages of coverage of 94-100 % of 4 different enterovirus serotypes in 73 % of the tested samples, representing the first whole-genome sequences of CV-A6/10/16 from Vietnam, and could assign correctly serotyping results in 100 % of 24 tested specimens. In all but three the obtained consensuses of two replicates from the same sample were 100 % identical, suggesting that our assay is highly reproducible. CONCLUSIONS: In conclusion, we have successfully developed a non-ribosomal rPCR and next-generation sequencing based assay for sensitive detection and direct whole-genome sequencing of HFMD pathogens from clinical samples.

The effect of the zeolite pore size on the Lewis acid strength of extra-framework cations.

The catalytic activity and the adsorption properties of zeolites depend on their topology and composition. For a better understanding of the structure-activity relationship it is advantageous to focus just on one of these parameters. Zeolites synthesized recently by the ADOR protocol offer a new possibility to investigate the effect of the channel diameter on the adsorption and catalytic properties of zeolites: UTL, OKO, and PCR zeolites consist of the same dense 2D layers (IPC-1P) that are connected with different linkers (D4R, S4R, O-atom, respectively) resulting in the channel systems of different sizes (14R × 12R, 12R × 10R, 10R × 8R, respectively). Consequently, extra-framework cation sites compensating charge of framework Al located in these dense 2D layers (channel-wall sites) are the same in all three zeolites. Therefore, the effect of the zeolite channel size on the Lewis properties of the cationic sites can be investigated independent of other factors determining the quality of Lewis sites. UTL, OKO, and PCR and pillared 2D IPC-1PI materials were prepared in Li-form and their properties were studied by a combination of experimental and theoretical methods. Qualitatively different conclusions are drawn for Li(+) located at the channel-wall sites and at the intersection sites (Li(+) located at the intersection of two zeolite channels): the Lewis acid strength of Li(+) at intersection sites is larger than that at channel-wall sites. The Lewis acid strength of Li(+) at channel-wall sites increases with decreasing channel size. When intersecting channels are small (10R × 8R in PCR) the intersection Li(+) sites are no longer stable and Li(+) is preferentially located at the channel-wall sites. Last but not least, the increase in adsorption heats with the decreasing channel size (due to enlarged dispersion contribution) is clearly demonstrated.

A comparison of salvage infusional chemotherapy regimens for recurrent/refractory multiple myeloma.

BACKGROUND: Despite the impact of proteasome inhibitors and immunomodulatory agents, infusional chemotherapy regimens continue to be used for patients with multiple myeloma. To the authors' knowledge, contemporary data regarding salvage chemotherapy regimens are sparse, with no direct comparisons. METHODS: The authors performed a single-institution study comparing 3 salvage chemotherapy regimens in 107 patients with recurrent/refractory multiple myeloma: dexamethasone, cyclophosphamide, etoposide, and cisplatin (DCEP) in 52 patients; bortezomib, thalidomide, dexamethasone, cisplatin, doxorubicin, cyclophosphamide, and etoposide (VTD-PACE) in 22 patients; and cyclophosphamide, vincristine, doxorubicin, and dexamethasone (CVAD) in 33 patients. RESULTS: Differences between treatment groups existed, including higher baseline creatinine for patients treated with CVAD (P<.001) and greater prior use of infusional chemotherapy for those receiving VTD-PACE (P<.001). There was no significant difference in response noted among the 3 regimens: 55% overall (P = .18). For the intent-to-transplant population, a similar percentage were successfully bridged to transplant without further therapy (62%; P = .9). There was no difference in survival observed across the 3 regimens, with an overall median progression-free survival of 4.5 months (95% confidence interval, 3.6-5.5 months [P = .8]) and a median overall survival of 8.5 months (95% confidence interval, 6.1-11 months [P = .8]). Furthermore, there was no statistically significant difference noted among clinically relevant adverse events, although there was a suggestion of fewer adverse events with DCEP. Patients treated with the intent to transplant had superior outcomes for response (odds ratio, 3.40; P = .01), progression-free survival (hazard ratio, 0.28; P<.001), and overall survival (hazard ratio, 0.19; P<.001). CONCLUSIONS: The 3 salvage regimens demonstrated similar responses, survival, and adverse events. Given the short response durations observed in the recurrent/refractory disease setting, infusional chemotherapy is best suited for cytoreduction before more definitive therapy is administered.

Clinical experience with an L-proline­stabilized 10 %intravenous immunoglobulin (Privigen®): real-life effectiveness and tolerability.

PURPOSE: This retrospective study evaluated the effectiveness and tolerability in clinical practice of an L-proline-stabilized 10 % intravenous immunoglobulin (IVIG; Privigen®) in patients with primary (PID) or secondary immunodeficiency (SID). METHODS: Patients from 6 centers in Europe and the US were treated with individually determined regimens of Privigen® for ≥3 months. Serum immunoglobulin G (IgG) trough levels, annualized rates of infection, hospitalization and antibiotics use, and the incidence of adverse events (AEs) were analyzed. RESULTS: Of 72 patients, three infants with severe combined immunodeficiency (SCID) were analyzed separately. The remaining 69 patients (52.2 % male; median age 38 years [range: 0.1-90.0]) with PID (82.6 %) or SID (17.4 %) received a mean (±standard deviation) Privigen® dose of 532 ± 250 mg/kg/month resulting in trough serum IgG levels of 407-1,581 mg/dL (median: 954 mg/dL). Ten patients (14.5 %) experienced 11 serious bacterial infections over 22.0 ± 15.0 months of treatment (0.087 events/patient/year, upper one-sided 99 % confidence interval: 0.170), the most common being pneumonia (11.6 %). The rates for any infection and hospitalization were 1.082 events/patient/year and 3.63 days/patient/year, respectively. Two patients with severe disease accounted for 303 of 460 hospital days. Across all 72 patients, 13 (18.1 %) patients experienced AEs, including 10 (13.9 %) patients with AEs at least possibly related to Privigen®, including headache (8.3 %), fever, and chills (2.8 % each). No related serious AEs were reported. One infant with SCID died due to severe viral infection. CONCLUSIONS: Despite the heterogeneous population, effectiveness and tolerability of Privigen® in clinical practice closely matched those reported in clinical studies.

Incidence and Epidemiology of Intussusception among Infants in Ho Chi Minh City, Vietnam.

OBJECTIVE: To evaluate rates of intussusception hospitalization among infants in Vietnam before the introduction of rotavirus vaccine. STUDY DESIGN: Between 2009 and 2011, we identified intussusception hospitalizations among infants using the International Statistical Classification of Diseases and Related Health Problems, 10th Revision, Clinical Modification code K56.1 at 2 large pediatric hospitals in Ho Chi Minh City, Vietnam that treat most of the intussusception cases in the city. We reviewed all medical records to confirm a Brighton level 1 case definition for intussusception. RESULTS: We identified a total of 869 intussusception cases in Ho Chi Minh City during the 3-year study period, for an annual rate of 296 per 100,000 infants. The mean age of intussusception was ∼ 37 weeks (8.6 months), with <2% of the cases occurring before age 15 weeks. Cases of intussusception were observed year-round in these hospitals with no evident seasonal pattern. Ultrasonography was used to diagnose most cases (97%), and reduction was performed by air enema in >95% of the cases, with only 1% of cases at 1 hospital and 5% at the other hospital requiring surgical intervention. Ultrasound diagnosis was confirmed by an independent radiologist in 94% of a randomly selected group of intussusception cases at 1 of the 2 hospitals. No mortality was reported. CONCLUSION: Vietnam has a substantially higher rate of intussusception in children aged >15 weeks compared with most other regions of the world. Most of our cases were diagnosed by ultrasound, and only a small proportion required surgical intervention with no fatalities, suggesting that the higher rates may be related in part to better and earlier detection of intussusception.

Measuring the Brønsted acid strength of zeolites--does it correlate with the O-H frequency shift probed by a weak base?

Brønsted-acid zeolites are currently being used as catalysts in a wide range of technological processes, spanning from the petrochemical industry to biomass upgrade, methanol to olefin conversion and the production of fine chemicals. For most of the involved chemical processes, acid strength is a key factor determining catalytic performance, and hence there is a need to evaluate it correctly. Based on simplicity, the magnitude of the red shift of the O-H stretching frequency, Δν(OH), when the Brønsted-acid hydroxyl group of protonic zeolites interacts with an adsorbed weak base (such as carbon monoxide or dinitrogen) is frequently used for ranking acid strength. Nevertheless, the enthalpy change, ΔH(0), involved in that hydrogen-bonding interaction should be a better indicator; and in fact Δν(OH) and ΔH(0) are often found to correlate among themselves, but, as shown herein, that is not always the case. We report on experimental determination of the interaction (at a low temperature) of carbon monoxide and dinitrogen with the protonic zeolites H-MCM-22 and H-MCM-56 (which have the MWW structure type) showing that the standard enthalpy of formation of OH···CO and OH···NN hydrogen-bonded complexes is distinctively smaller than the corresponding values reported in the literature for H-ZSM-5 and H-FER, and yet the corresponding Δν(OH) values are significantly larger for the zeolites having the MWW structure type (DFT calculations are also shown for H-MCM-22). These rather unexpected results should alert the reader to the risk of using the O-H frequency shift probed by an adsorbed weak base as a general indicator for ranking zeolite Brønsted acidity.