PTPROt: an alternatively spliced and developmentally regulated B-lymphoid phosphatase that promotes G0/G1 arrest.

Protein tyrosine phosphatases (PTP) regulate the proliferation, differentiation, and viability of lymphocytes by modulating their signaling pathways. By using the differential display assay, we have cloned a putative receptor-type PTP, which is predominantly expressed in B-lymphoid tissues (lymph nodes and spleen). This PTP, termed PTPROt (truncated), is a tissue-specific alternatively-spliced form of a human epithelial PTP, PTPRO (PTPU2/GLEPP1). Whereas the epithelial PTPRO includes an approximately 800-amino acid extracellular domain, the major (3 kb) PTPROt cDNA predicts a unique 5' untranslated region and truncated (8 amino acids) extracellular domain with a conserved transmembrane region and single catalytic domain. PTPROt cDNAs encode functional approximately 47-kD and approximately 43-kD PTPs, which are most abundant in normal naive quiescent B cells and decreased or absent in germinal center B cells and germinal center-derived diffuse large B-cell lymphomas. Because PTPROt was predominantly expressed in naive quiescent B cells, the enzyme's effects on cell-cycle progression were examined. When multiple stable PTPROt sense, antisense, and vector only B-cell transfectants were grown in reduced serum and synchronized with nocodazole, PTPROt sense clones exhibited markedly increased G0/G1 arrest. Taken together, these data implicate PTPROt in the growth control of specific B-cell subpopulations.     

Racial disparities in family-provider interactions for pediatric asthma care

Objective: Black and Latino children experience significantly worse asthma morbidity than their white peers for multifactorial reasons. This study investigated differences in family-provider interactions for pediatric asthma, based on race/ethnicity. Methods: This was a cross-sectional study of parent surveys of asthmatic children within the Population-Based Effectiveness in Asthma and Lung Diseases Network. Our study population comprised 647 parents with survey response data. Data on self-reported race/ethnicity of the child were collected from parents of the children with asthma. Outcomes studied were responses to the questions about family-provider interactions in the previous 12 months: (1) number of visits with asthma provider; (2) number of times provider reviewed asthma medications with patient/family; (3) review of a written asthma treatment plan with provider; and (4) preferences about making asthma decisions. Results: In multivariate adjusted analyses controlling for asthma control and other co-morbidities, black children had fewer visits in the previous 12 months for asthma than white children: OR 0.63 (95% CI 0.40, 0.99). Additionally, black children were less likely to have a written asthma treatment plan given/reviewed by a provider than their white peers, OR 0.44 (95% CI 0.26, 0.75). There were no significant differences by race in preferences about asthma decision-making nor in the frequency of asthma medication review. Conclusion: Black children with asthma have fewer visits with their providers and are less likely to have a written asthma treatment plan than white children. Asthma providers could focus on improving these specific family-provider interactions in minority children.     

Role of coronary physiology in the contemporary management of coronary artery disease

Coronary artery disease (CAD) remains the leading cause of death worldwide with approximately 1 in 30 patients with stable CAD experiencing death or acute myocardial infarction each year. The presence and extent of resultant myocardial ischaemia has been shown to confer an increased risk of adverse outcomes. Whilst, optimal medical therapy (OMT) forms the cornerstone of the management of patients with stable CAD, a significant number of patients present with ischaemia refractory to OMT. Historically coronary angiography alone has been used to determine coronary lesion severity in both stable and acute settings. It is increasingly clear that this approach fails to accurately identify the haemodynamic significance of lesions; especially those that are visually “intermediate” in severity. Revascularisation based upon angiographic appearances alone may not reduce coronary events above OMT. Technological advances have enabled the measurement of physiological indices including the fractional flow reserve, the index of microcirculatory resistance and the coronary flow reserve. The integration of these parameters into the routine management of patients presenting to the cardiac catheterization laboratory with CAD represents a critical adjunctive tool in the optimal management of these patients by identifying patients that would most benefit from revascularisation and importantly also highlighting patients that would not gain benefit and therefore reducing the likelihood of adverse outcomes associated with coronary revascularisation. Furthermore, these techniques are applicable to a broad range of patients including those with left main stem disease, proximal coronary disease, diabetes mellitus, previous percutaneous coronary intervention and with previous coronary artery bypass grafting. This review will discuss current concepts relevant to coronary physiology assessment, its role in the management of both stable and acute patients and future applications.     

Correction of skeletal class III in a growing male patient by reverse pull facemask

The following case report describes the management of a 6-year-old male patient in early mixed dentition with a mesial step molar relation, an anterior reverse overjet, and skeletal Class III due to a slightly deficient maxilla. The treatment plan included protraction of the maxilla by a reverse pull Petit type facemask for 10 months followed by 15 months of active retention by a Frankel III appliance.     

Cellular fibronectin stimulates hepatocytes to produce factors that promote alcohol-induced liver injury

AIM:To examine the consequences of cellular f ibronectin(cFn)accumulation during alcohol-induced injury,and inv estigate whether increased cFn could have an effect on hepatocytes(HCs)by producing factors that could cont ribute to alcohol-induced liver injury.METHODS:HCs were isolated from rats fed a control or ethanol liquid diet for four to six weeks.Exogenous c Fn(up to 7.5 μg/mL)was added to cells cultured for 20 h,and viability(lactate dehydrogenase),apoptosis(caspase activity)and se cretion of proinflammat-ory cytokines(tumor ne c rosis fac tor alpha,TNF-α and interleukin 6,IL-6),mat rix metalloproteinases(MMPs)and their inhibitors(tissue inhibitors of metall-oproteinases,TIMPs)was det ermined.Degrad ation of iodinated cFn was det ermined over a 3 h time period in the preparations.RESULTS:cFn degradation is impaired in HCs isolated from ethanol-fed animals,leading to its accumulation in the matrix.Addition of exogenous cFn did not affect viability of HCs from control or ethanolfed animals,and apoptosis was affected only at the higher concentration.Sec retion of MMPs,TIMPs,TNF-α and IL-6,however,was increased by exogenously added cFn,with HCs from ethanolfed animals showing increased susceptibility compared to the controls.CONCLUSION:These results suggest that the elevated amounts of cFn observed in alcoholic liver injury can stimulate hepatocytes to produce factors which promote further tissue damage.     

Temporomandibular joint adaptations following two-phase therapy: an MRI study

Authors – Wadhawan N, Kumar S, Kharbanda OP, Duggal R, Sharma R Aim – To document the alterations within the condyle‐glenoid fossa (C‐GF) complex and the positional changes of the glenoid fossa in the cranium after removable functional appliance therapy and after the completion of fixed appliance therapy. Setting and Sample – The Department of Orthodontics, Centre for Dental Education and Research, All India Institute of Medical Sciences, New Delhi, India. The study sample consisted of 12 growing children (eight girls and four boys) between 10 and 14 years of age with skeletal Class II division 1 malocclusion selected on well defined criteria. Materials and Methods – All patients were treated with either the Twin Block or the Bionator appliance followed by fixed appliances. Mean total treatment duration was 28 months. The changes in and around the C‐GF complex were evaluated using MRI at pre‐treatment stage, after functional appliance therapy and at the completion of fixed mechanotherapy. Results – Forward condylar position within the glenoid fossa and articular disc retrusion with respect to the condylar head were statistically significant after functional appliance therapy. However, the condyles had a relatively concentric position within the glenoid fossa, while the articular disc resumed its pre‐treatment position at the end of the treatment. Linear measurements from the centre of the external auditory meatus to the post‐glenoid spine revealed a 1.3‐mm forward relocation of the post‐glenoid spine along the Frankfurt Horizontal plane. Conclusions – Forward relocation of the C‐GF complex seems to be one of the mechanisms of action of functional appliances, while the internal anatomic arrangement within the temporomandibular joint (TMJ) complex normalizes to its pre‐treatment position.     

Changes in Tdap and MCV4 Vaccine Coverage Following Enactment of a Statewide Requirement of Tdap Vaccination for Entry Into Sixth Grade

Objectives. We evaluated changes in tetanus toxoid, reduced diptheria toxoid, acellular pertussis (Tdap), and tetravalen meningococcal (MCV4) vaccine coverage following enactment of a New York State mandate requiring Tdap before entering sixth grade.Methods. Using data from a hospital-based immunization registry, we measured Tdap and MCV4 coverage among youths aged 11 to 14 years in New York City at 3 time points: premandate, mandate year 1, and mandate year 2.Results. Among overlapping cohorts of 4316 (premandate), 4131 (mandate year 1), and 3639 (mandate year 2) youths, Tdap coverage increased steadily over time (29%, 58%, and 83%, respectively). Increases were observed among all ages. Across the same time points, MCV4 coverage also increased (10%, 30%, and 60%, respectively). Most adolescents did not receive MCV4 during the same visit they received Tdap.Conclusions. A Tdap school-entry mandate was associated with substantial increases in immunization coverage, even in age groups not directly affected by the mandate. At the postmandate time points, MCV4 coverage remained lower than Tdap coverage. Provider education should emphasize the importance of reviewing vaccine records and administering all recommended vaccines at every clinical encounter.In recent years, new vaccines against pertussis¹ and meningitis² have been introduced to the routine immunization schedule for children and adolescents. Both are recommended for youths aged 11 to 12 years, with catch-up vaccination for older adolescents. Pertussis is a highly contagious infection, often causing school or community outbreaks. Among healthy adolescents, pertussis is usually a self-limited illness characterized by a prolonged cough. However, secondary complications can occur, and adolescents serve as an important reservoir for transmission to infants, for whom infection can lead to pneumonia, respiratory failure, apnea, and even death.³ The tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine has been shown to be 92% effective in preventing culture-confirmed pertussis.⁴Adolescents, and specifically those in crowded living conditions, have been shown to be at increased risk for N. meningitides infection.⁵ N. meningitides is highly contagious and can cause meningitis, septicemia, and death. The tetravalent meningococcal polysaccharide-protein conjugate (MCV4) vaccine has been shown to be safe and highly immunogenic in protecting against N. meningitides infection.⁶Although the Tdap and MCV4 vaccines hold great promise, achieving high immunization coverage among adolescents remains a challenge. Barriers to adolescent immunization include failure to present for medical services, missed immunization opportunities, and scattered immunization records.⁷ Few adolescents report the receipt of annual preventive health visits,⁸ so reviewing immunization status and immunizing at every clinical encounter is key to increasing vaccine coverage in this population. Results of the 2008 National Immunization Survey–Teen indicate that among adolescents aged 13 to 17 years, nationwide coverage for Tdap and MCV4 remains low (41% and 42%, respectively).⁹Mandates requiring immunization prior to school entry have been highly effective in increasing immunization coverage.^10–14 In 1 study, hepatitis B immunization rates increased from 13% to 71% following implementation of a middle school mandate.¹⁵ Mandates were initially used to promote the uptake of vaccines for highly contagious infectious diseases and thus to prevent school-based outbreaks, but today many states mandate vaccines for diseases that are not communicable (tetanus) or that are communicable primarily through sexual or blood exposures (hepatitis B). Recent controversy regarding mandates for the human papillomavirus vaccine has resulted in significant backlash against mandates,^16–18 highlighting the need for states to be judicious in their decisions to implement new mandates.Although mandates are known to rapidly increase vaccine coverage in their target population, there is little evidence of any carryover benefits. No studies to date have evaluated whether a new mandate will result in improved vaccine coverage for nonmandated age groups or for other nonmandated, age-appropriate vaccines. In the fall of 2007, New York State became one of the first states to require Tdap prior to entering sixth grade. This situation provided a unique opportunity to observe postmandate changes in coverage for Tdap (the mandated vaccine) and MCV4 (a nonmandated, recommended vaccine) across multiple age groups.