Induction of protective immunity by synthetic Vibrio cholerae hexasaccharide derived from V. cholerae O1 Ogawa lipopolysaccharide bound to a protein carrier

Synthetic antigens that mimic the terminal hexasaccharide epitope of the O-specific polysaccharide of Vibrio cholerae O1, serotype Ogawa, were conjugated to bovine serum albumin (BSA). Conjugates with carbohydrate-to-carrier molar ratios of 15.5:1, 9.2:1, and 4.6:1 were tested for immunogenicity and efficacy in mice. The role of preimmunity to BSA and the use of adjuvant in the generation of the serologic response to the O-specific polysaccharide and protection against virulent V. cholerae was examined. Preimmunity to BSA did not affect the anti-Ogawa titers but seemed to enhance the protective capacity of antiserum. All 3 conjugates were immunogenic, but adjuvant was effective at inducing higher and earlier antibody responses. In tertiary serum samples, a correlation was found between vibriocidal activity and protection. The protective capacity of antiserum was evident in serum from mice immunized with all conjugates, but it was highest in the groups that received the conjugate with the lowest level of substitution. Further studies are required to increase understanding of the reason for differential protection.     

Third-generation,self-inactivating gp91(phox) lentivector corrects the oxidase defect in NOD/SCID mouse-repopulating peripheral blood-mobilized CD34+ cells from patients with X-linked chronic granulomatous disease

HIV-1-derived lentivectors are promising for gene transfer into hematopoietic stem cells but require preclinical in vivo evaluation relevant to specific human diseases. Nonobese diabetic/severe combined immunodeficient (NOD/SCID) mice accept human hematopoietic stem cell grafts, providing a unique opportunity for in vivo evaluation of therapies targeting human hematopoietic diseases. We demonstrate for the first time that hematopoietic stem cells from patients with X-linked chronic granulomatous disease (X-CGD) give rise to X-CGD-phenotype neutrophils in the NOD/SCID model that can be corrected using VSV-G-pseudotyped, 3rd-generation, self-inactivating (SIN) lentivector encoding gp91(phox). We transduced X-CGD patient-mobilized CD34(+) peripheral blood stem cells (CD34(+)PBSCs) with lentivector-gp91(phox) or amphotropic oncoretrovirus MFGS-gp91(phox) and evaluated correction ex vivo and in vivo in NOD/SCID mice. Only lentivector transduced CD34(+)PBSCs under ex vivo conditions nonpermissive for cell division, but both vectors performed best under conditions permissive for proliferation (multiple growth factors). Under the latter conditions, lentivector and MFGS achieved significant ex vivo correction of X-CGD CD34(+)PBSCs (18% and 54% of cells expressing gp91(phox), associated with 53% and 163% of normal superoxide production, respectively). However, lentivector, but not MFGS, achieved significant correction of human X-CGD neutrophils arising in vivo in NOD/SCID mice that underwent transplantation (20% and 2.4%, respectively). Thus, 3rd-generation SIN lentivector-gp91(phox) performs well as assessed in human X-CGD neutrophils differentiating in vivo, and our studies suggest that the NOD/SCID model is generally applicable for in vivo study of therapies evaluated in human blood cells expressing a specific disease phenotype.     

Different C-reactive protein kinetics in post-operative hip-fractured geriatric patients with and without complications

BACKGROUND: Hip fracture is a frequent injury in the elderly, and is associated with a high incidence of functional impairment, complications and mortality. OBJECTIVE: To determine kinetics of C-reactive protein (CRP), fibrinogen and erythrocyte sedimentation rate (ESR) in hip-fractured patients over a 1-month post-operative period; to examine the relationship of these parameters to cognition, operation type, post-operational complications, functional level 1 month post-operatively and 6-month mortality. METHODS AND SUBJECTS: 32 aged patients operated on for hip fracture were prospectively followed-up for 6 months. Fracture, type of operation and anesthetic risk were recorded. Cognition was evaluated by the Mini-Mental State Examination and pre-fracture functional level evaluated by the Katz Index of ADL. Follow-up included complications, mortality and functional outcome. CRP, fibrinogen and ESR were assessed during the first 10 h post-fracture; 48-60 h, and 7 and 30 days post-operatively, respectively. RESULTS: Only CRP kinetics were found to differ in patients with complications vs. those without, as a group (p = 0.006), and in patients suffering infections, delirium and cardiovascular complication vs. patients with no complications (p = 0.06, 0.03, 0.02, respectively). Mean (+/-SEM) CRP 48-60 h post-operatively was 20.9 +/- 2.1 and 13.1 +/- 1.6 mg/dl in complicated and uncomplicated patients, respectively (p = 0.002). The mean CRP 48-60 h post-operatively was highly correlated with the CRP area under the curve, R = 0.88 (p < 0.001). A cut-off level of 15 mg/dl for CRP, 48- 60 h post-operatively, was calculated for patients with complications (sensitivity 93%, specificity 65%, p = 0.003). CRP, fibrinogen and ESR were not related to fracture or type of operation, cognition, anesthetic risk, 1-month post-operative functioning and 6-month mortality. CONCLUSIONS: CRP measurement in elderly patients operated for hip fracture may be valuable in assessing and monitoring complications.     

Prognostic factors and efficacy of different chemotherapeutic regimens in patients with mediastinal nonseminomatous germ cell tumors

Purpose

Patients (pts) with mediastinal nonseminomatous germ cell tumors (MNGCT) are belonged to poor prognostic group by IGCCCG. We retrospectively studied the prognostic factors and efficacy of different chemotherapeutic regimen in pts with MNGCT.

Methods

We analyzed data on 61 pts with MNGCT. Conditional induction chemotherapy BEP was performed in 38 %, TBEP—in 28 %, CBOP—in 28 %, accelerated (two weekly) version of BEP—in 6 % pts. Based on similar efficacy of CBOP and TBEP regimens, we combines pts with CPOB and TBEP regimen in one group—55.8 % and different variants of BEP regimen in the second group—44.2 %. Multivariate Cox regression analysis was performed to determine independent factors, which influenced on overall survival.

Results

We revealed the following independent negative prognostic factors: age ≥24 years (p = 0.07), size of the primary mediastinal tumor ≥19 cm (p = 0.03). Median overall survival (OS) has not been reached, and 2-year OS was 66 % in pts with good prognosis (age <24 years and/or size of mediastinal tumor <19 cm) versus 15 months and 40 % in pts with poor prognosis (p = 0.03). Objective marker negative response was revealed more often in pts with CPOB/TBEP group: 26/34 (76.5 %) versus 14/27 (52 %), p = 0.08. Median OS was also higher in pts with CPOB/TBEP group: nonreached versus 15 months (p = 0.01).

Conclusion

CPOB and TBEP regimen were significantly associated with better outcome in pts with MNGCT. Age ≥24 years and size of the primary mediastinal tumor ≥19 cm were found as independent negative prognostic factors.     

Significant disparity in base and sugar damage in DNA resulting from neutron and electron irradiation

In this study, a comparison of the effects of neutron and electron irradiation of aqueous DNA solutions was investigated to characterize potential neutron signatures in DNA damage induction. Ionizing radiation generates numerous lesions in DNA, including base and sugar lesions, lesions involving base–sugar combinations (e.g. 8,5′-cyclopurine-2′-deoxynucleosides) and DNA–protein cross-links, as well as single- and double-strand breaks and clustered damage. The characteristics of damage depend on the linear energy transfer (LET) of the incident radiation. Here we investigated DNA damage using aqueous DNA solutions in 10 mmol/l phosphate buffer from 0–80 Gy by low-LET electrons (10 Gy/min) and the specific high-LET (∼0.16 Gy/h) neutrons formed by spontaneous ²⁵²Cf decay fissions. 8-hydroxy-2′-deoxyguanosine (8-OH-dG), (5′R)-8,5′-cyclo-2′-deoxyadenosine (R-cdA) and (5′S)-8,5′-cyclo-2′-deoxyadenosine (S-cdA) were quantified using liquid chromatography–isotope-dilution tandem mass spectrometry to demonstrate a linear dose dependence for induction of 8-OH-dG by both types of radiation, although neutron irradiation was ∼50% less effective at a given dose compared with electron irradiation. Electron irradiation resulted in an exponential increase in S-cdA and R-cdA with dose, whereas neutron irradiation induced substantially less damage and the amount of damage increased only gradually with dose. Addition of 30 mmol/l 2-amino-2-(hydroxymethyl)-1,3-propanediol (TRIS), a free radical scavenger, to the DNA solution before irradiation reduced lesion induction to background levels for both types of radiation. These results provide insight into the mechanisms of DNA damage by high-LET ²⁵²Cf decay neutrons and low-LET electrons, leading to enhanced understanding of the potential biological effects of these types of irradiation.     

Mathematical Modeling and Experimental Substantiation of the Gas Release Process in the Production of Non-Autoclaved Aerated Concrete

The widespread use of aerated concrete in construction has led to the emergence of many types and compositions. However, additional research should fill theoretical gaps in the phenomenon of gas release during the formation of the structure of aerated concrete. Based on theoretical analysis and experimental studies, the article proposes a mathematical model of the swelling process based on the physicochemical laws of convection and molecular diffusion of hydrogen from a mixture and the conditions of swelling, precipitation, and stabilization of the mixture. An improved method for the manufacture of aerated concrete is proposed, which consists of introducing cement pre-hydrated for 20–30 min into the composition of the aerated concrete mixture and providing improved gas-holding capacity and increased swelling of the mixture, reducing the average density of aerated concrete up to 29% and improving heat-shielding properties up to 31%. At the same time, the small dynamics of a decrease in the strength properties of aerated concrete were observed, which is confirmed by an increased structural quality factor (CSQ) of up to 13%. As a result, aerated concrete has been obtained that meets the requirements of environmental friendliness and has improved mechanical and physical characteristics. Economic efficiency is to reduce the cost of production of aerated concrete and construction in general by about 15%.     

Abdominal compartment syndrome after laparoscopic salpingectomy for ectopic pregnancy

Abdominal compartment syndrome is a consequence of increased intraabdominal pressure. It can be triggered by inflammation, hemorrhage, chemical peritonitis, or prolonged insufflations during laparoscopy. It is a well-known phenomenon for intensive care specialists, but gynecologists are relatively unfamiliar with its occurrence. A woman with heterotopic pregnancy underwent urgent laparoscopy because of abdominal hemorrhage. The postoperative course was complicated by abdominal pain, ascites, bowel dysfunction, and renal failure, which resolved rapidly after catheterization and paracentesis. In this case, abdominal compartment syndrome developed after unremarkable laparoscopy, and appeared to be triggered by change of progesterone formulation. Decompression by paracentesis was lifesaving, and led to rapid resolution of the symptoms.     

Vertebral hemangiomas: diagnosis, management, natural history and clinicopathological correlates in 86 patients

BACKGROUND Vertebral hemangiomas are characterized by diverse clinical histories, radiological features, and results of surgical treatment. It still remains unclear how these differences in clinical behavior relate to pathological type.

METHODS A retrospective diagnostic, surgical, and histopathological study of 86 consecutive patients with various pathological types of vertebral hemangioma was performed to establish clinicopathological correlates.

RESULTS The study confirmed that differences exist in clinical course, appearance on imaging, and outcomes in pathological types of hemangiomas. Based on these findings the authors attempted to identify signs characterizing each group.

CONCLUSIONS Differences in clinical history and radiological features exist among pathological types of vertebral hemangiomas. These differences cannot precisely predict the type pathology before histologic examination, but do help us to understand the natural history of such lesions more fully.