Vaccination with chimeric protein induces protection in murine model against ascariasis

An estimated 400 million people are infected by parasites of the genus Ascaris and the existing control measures are inefficient. Vaccine development using B cell antigens is a promising strategy for increased protection against this parasite. The present study aimed at developing a chimeric protein capable of conferring protection against infection by Ascaris sp. For this purpose, we performed B-cell epitope predictions on previously described vaccine candidate proteins from Ascaris suum and the corresponding peptides were used to construct a chimeric protein. Female BALB / c mice were immunized subcutaneously in three doses at 10 day intervals with a vaccine formulation comprised of the chimeric protein together with monophosphoryl lipid A (MPLA). Control groups included protein alone, MPLA, or PBS. After challenge infection, animals vaccinated with chimeric protein plus MPLA showed a reduction of 73.54% of larval load in the lung compared to control group animals. Animals immunized with chimeric protein plus MPLA also display higher IgG response and a reduction in lung inflammation. Our study highlights how chimeric proteins containing more than one B cell epitope can enhance immune protection against helminthic infection and offer new approaches to the development of Ascaris vaccines.     

Zarit burden interview among caregivers of community-dwelling older adults in a caribbean setting (Jamaica): Reliability and factor structure

The Zarit Burden Interview has been the most popularly used tool for measuring caregiver burden and with the 60 years and over population in Jamaica and developing countries expected to increase, caregiver burden and its assessment assume increased importance. Establishing the reliability and underlying factor structure of instruments such as the ZBI is critical. This study sought to determine the reliability of the Zarit Burden Interview and to assess its underlying factor structure. The ZBI was administered to 180 caregivers of community dwelling older persons in Jamaica in a nationally representative sample across four geographic health regions in 2016. The factor structure was identified using exploratory factor analysis (EFA) with Varimax rotation. Cronbach's alpha was used to assess internal consistency/reliability of the instrument. The internal consistency/reliability of the ZBI instrument was high (Cronbach's α = 0.859) and the corrected item-total correlations ranged from 0.134 to 0.730. The ZBI mean score was found to be 16.92 ± 12.04. EFA produced a six-factor model comprised of 19 items which explained 48.97% of total variance, and was subsequently reduced to four (37.27% of total variance) via the use of parallel analysis and scrutiny of confidence intervals. The four factors identified were ‘personal strain’, ‘social relations disruption’, ‘resource strain/imbalance’ and ‘role intensity’. The ZBI-22 tool is a reliable instrument for evaluating caregiver burden among community dwelling older persons in Jamaica. A four factor model has emerged providing greater insights on the underlying constructs of the ZBI, the most widely used caregiver burden assessment tool.     

Short-term chemoprophylaxis with ceftizoximevs. Five-day aminoglycoside with metronidazole in ‘contaminated’ lower gastrointestinal surgery

In a prospective, open, randomized controlled trial, 173 patients requiring surgery for potentially contaminated lower gastrointestinal surgery were allocated to receive either two doses of ceftizoxime (2 gm) with one dose of metronidazole (1.5 gm) or gentamicin 3 mg/kg/day for five days with one dose of metronidazole (1.5 gm). Eighty-nine patients received ceftizoxime and 84 patients received gentamicin. The groups were comparable with respect to diagnosis, procedure, type of anastomosis, and wound closure. The incidence of withdrawal due to failure to respond to the study drug (11.5 percent) was equivalent in the two groups. There was no difference in the overall incidence of postsurgical infection between the ceftizoxime and metronidazole group (22.2 percent) and the gentamicin and metronidazole group (25.7 percent). The incidence of wound infection (ceftizoxime and metronidazole, 6.9 percent; gentamicin and metronidazole, 10 percent) and deep sepsis (ceftizoxime and metronidazole, 15.3 percent; gentamicin and metronidazole, 15.7 percent) was similar.     

A factor analysis of the Klein sexual orientation Grid in two disparate samples

Many researchers interested in sexual orientation can be separated into two camps: The lumpers, who try to reduce sexual classifications to as small a number of categories as possible, and the splitters, who try to show differences among groups and individuals that make classification schemes increasingly difficult and/or intricate. We report factor analyses of the Klein Grid (a questionnaire with 21 sexual orientation items) to see how many factors emerge in two samples of strikingly different origins. In both samples, the first factor to emerge loaded substantially on all of the Klein Grid's 21 items. This factor accounted for a majority of the variance. In both samples, a second, correlated factor emerged which indexed a separation between most of the items and those having to do with social and/or emotional preferences. In both samples, a third correlated factor also emerged, but this factor differed between the two populations: one refined the social/emotional distinction and the other distinguished ideal behavior from past and current behavior. We conclude on the basis of our analysis that both the lumpers and the splitters are correct.Supported by NIMH grants IP50 MH 45294 and R01 MH 43298.     

Caesarean section and phaeochromocytoma resection in a patient with Von Hippel Lindau disease

This report describes the anaesthetic management of a women with a term gestation, Von Hippel Lindau disease (VHLD), and a phaeochromocytoma, scheduled for a combined phaeochromocytoma resection and Caesarean section. Von Hippel Lindau disease is characterized by diffuse haemangioblastomas of the central nervous system (CNS) and viscera. It is also associated with phaeochromocytomas and renal cell carcinomas. Patients frequently have asymptomatic spinal cord and intracranial pathology. The patient and her fetus presented a challenge because of the anaesthetic restrictions imposed by VHLD, and her pregnancy. She was also at risk of developing malignant hypertension from the phaeochromocytoma. The patient was not a candidate for regional anaesthesia because of the possibility of spinal cord haemangioblastomas. She had received adrenergic blockade with phentolamine (total 30 mg a day) and propranolol (total 40 mg a day) since the 27th wk of gestation in order to control hypertension secondary to the phaeochromocytoma. General anaesthesia was administered with aggressive management of hypertension with adrenergic blockers (labetalol 1.0 mg · kg^?1 and esmolol 0.75 mg · kg^?1) and sodium nitroprusside 1.5 μg · kg^?1 (total). Before delivery of the baby, opioids, which could have resulted in a fetus with CNS depression, were avoided. After delivery, opioids (sufentanil 0.4 ng · kg^?1 hr^?1) were used to limit the use of inhalational anaesthesia which may contribute to uterine atony. Postoperative pain was managed with an intravenous narcotic infusion. Both patients had uneventful postoperative courses.     

Surgical pitfalls in a patient with type IV Ehlers-Danlos syndrome and spontaneous colonic rupture

PURPOSE: This paper intends to stress the importance of early diagnosis and discuss surgical treatment of Type IV Ehlers-Danlos syndrome (EDS-4), an autosomal dominant connective tissue disease characterized by typical features of the face and extremities, inappropriate and easy bruising, and extreme tissue fragility, which may lead to dramatic and often fatal complications, mostly spontaneous arterial or intestinal rupture. METHODS: We report the case of a 41-year-old female who presented with spontaneous perforation of the sigmoid colon. RESULTS: The patient was seen over a nine-year period, during which time she required six operations and presented with a great number of surgical complications including stenosis of an end-colostomy, repeated subocclusive episodes caused by intraperitoneal adhesions, and enterocutaneous fistulas, finally ending with an ileostomy and short bowel syndrome. It is only after a difficult laparotomy for ovarian cyst excision, marked by numerous adhesions and friable bowel, that the diagnosis of EDS-4 was considered and established. CONCLUSIONS: In case of “idiopathic” spontaneous perforation of the colon in a young adult, features of EDS-4 should be thoroughly looked into and, if found, skin fibroblast culture with collagen Type III analysis performed. The surgical treatment of choice consists of subtotal colectomy and permanent endileostomy. In case of patient refusal, a second-stage ileorectal anastomosis can be performed but carries the high risk of anastomotic leakage.     

The Massachusetts Behavioral Health Program Year 5: Transition to a New Managed Care Organization

Year 5 of the Massachusetts Behavioral Health Program was a transition to management by a new private managed care organization. Fifty-eight providers interviewed for an ongoing panel survey reported slightly lower levels of quality, access, utilization, and length of stay than a year earlier. Relationships with providers and advocates improved after an initial difficult period, while consumer and family involvement at all levels remained low. The greatest changes in managed care appeared to take place during the initial transition from fee-for-service care, but intractable problems continue, and full participation of stakeholders seems difficult to achieve.     

Studentschool bonding and adolescent problem behavior

Adolescent problem behavior, including substance use, schoolmisconduct and delinquency, is a national concern. Implicitin the concept of middle school is the recognition that studentswho develop positive social bonds with their school are morelikely to perform well academically, and refrain from misconductand other antisocial behavior. However, little scientific attentionhas been given to the complex interactions between middle schoolstudents and the school environment. Prior to implementing amiddle school problem behavior prevention program we conducteda survey in the seven middle schools in one US school district.Out of 4668 grade 6–8 students enrolled, 4263 (91.3%)completed the survey. Student–school bonding was positivelycorrelated with school adjustment (r = 0.49) and perceived schoolclimate (r = 0.77), but inversely correlated with problem behavior(r = –0.39 to –0.43). Problem behavior was significantlyhigher (P < 0.001) among males than females and among studentsin higher grades. Conversely, school bonding, climate and adjustmentwere significantly higher (P < 0.001) among females thanmales, but declined significantly from one grade to the next.The data support the conclusion that school bonding is associatedwith problem behavior. We describe the development of a multiple-componentintervention in middle schools designed to increase student–schoolbonding and prevent problem behavior.     

Anti-Angiogenic Activity of Selected Receptor Tyrosine Kinase Inhibitors, PD166285 and PD173074: Implications for Combination Treatment with Photodynamic Therapy

Angiogenesis, the formation of new blood vessels from an existing vasculature, is requisite for tumor growth. It entails intercellular coordination of endothelial and tumor cells through angiogenic growth factor signaling. Interruption of these events has implications in the suppression of tumor growth. PD166285, a broad-spectrum receptor tyrosine kinase (RTK) inhibitor, and PD173074, a selective FGFR₁TK inhibitor, were evaluated for their anti-angiogenic activity and anti-tumor efficacy in combination with photodynamic therapy (PDT). To evaluate the anti-angiogenic and anti-tumor activities of these compounds, RTK assays, in vitro tumor cell growth and microcapillary formation assays, in vivo murine angiogenesis and anti-tumor efficacy studies utilizing RTK inhibitors in combination with photodynamic therapy were performed. PD166285 inhibited PDGFR--, EGFR-, and FGFR₁TKs and c-src TK by 50% (IC₅₀) at concentrations between 7–85nM. PD173074 displayed selective inhibitory activity towards FGFR₁TK at 26nM. PD173074 demonstrated (>100 fold) selective growth inhibitory action towards human umbilical vein endothelial cells compared with a panel of tumor cell lines. Both PD166285 and PD173074 (at 10nM) inhibited the formation of microcapillaries on Matrigel-coated plastic. In vivo anti-angiogenesis studies in mice revealed that oral administration (p.o.) of either PD166285 (1–25 mg/kg) or PD173074 (25–100 mg/kg) generated dose dependent inhibition of angiogenesis. Against a murine mammary 16c tumor, significantly prolonged tumor regressions were achieved with daily p.o. doses of PD166285 (5–10 mg/kg) or PD173074 (30–60 mg/kg) following PDT compared with PDT alone (p<0.001). Many long-term survivors were also noted in combination treatment groups. PD166285 and PD173074 displayed potent anti-angiogenic and anti-tumor activity and prolonged the duration of anti-tumor response to PDT. Interference in membrane signal transduction by inhibitors of specific RTKs (e.g. FGFR₁TK) should result in new chemotherapeutic agents having the ability to limit tumor angiogenesis and regrowth following cytoreductive treatments such as PDT.