Synaptic-dependent developmental dysconnectivity in 22q11.2 deletion syndrome.

Chromosome 22q11.2 deletion is among the strongest known genetic risk factors for neuropsychiatric disorders, including autism and schizophrenia. Brain imaging studies have reported disrupted large-scale functional connectivity in people with 22q11 deletion syndrome (22q11DS). However, the significance and biological determinants of these functional alterations remain unclear. Here, we use a cross-species design to investigate the developmental trajectory and neural underpinnings of brain dysconnectivity in 22q11DS. We find that LgDel mice, an established mouse model of 22q11DS, exhibit age-specific patterns of functional MRI (fMRI) dysconnectivity, with widespread fMRI hyper-connectivity in juvenile mice reverting to focal hippocampal hypoconnectivity over puberty. These fMRI connectivity alterations are mirrored by co-occurring developmental alterations in dendritic spine density, and are both transiently normalized by developmental GSK3ß inhibition, suggesting a synaptic origin for this phenomenon. Notably, analogous hyper- to hypoconnectivity reconfiguration occurs also in human 22q11DS, where it affects hippocampal and cortical regions spatially enriched for synaptic genes that interact with GSK3ß, and autism-relevant transcripts. Functional dysconnectivity in somatomotor components of this network is predictive of age-dependent social alterations in 22q11.2 deletion carriers. Taken together, these findings suggest that synaptic-related mechanisms underlie developmentally mediated functional dysconnectivity in 22q11DS.

Distinctive gut microbiomes of ankylosing spondylitis and inflammatory bowel disease patients suggest differing roles in pathogenesis and correlate with disease activity.

BACKGROUND: Multiple studies have confirmed dysbiosis in ankylosing spondylitis (AS) and inflammatory bowel disease (IBD); however, due to methodological differences across studies, it has not been possible to determine if these diseases have similar or different gut microbiomes. RESULTS: In this study, faecal and intestinal biopsies were obtained from 33 Australian AS patients (including 5 with concomitant IBD, 'AS-IBD'), 59 IBD patients and 105 healthy controls. Stool samples were also obtained from 16 Italian AS patients and 136 Swedish AS patients. Focusing on the Australian cohort, AS, AS-IBD and IBD patients differed from one another and from healthy controls in both alpha and beta diversity. AS patients with and without clinical IBD could be distinguished from one another with moderate accuracy using stool microbiome (AUC=0.754). Stool microbiome also accurately distinguished IBD patients from healthy controls (AUC=0.757). Microbiome composition was correlated with disease activity measured by BASDAI and faecal calprotectin (FCP) levels. Enrichment of potentially pathogenic Streptococcus was noted in AS, AS-IBD and IBD patients. Furthermore, enrichment of another potentially pathogenic genus, Haemophilus, was observed in AS, AS-IBD, IBD, AS patients with increased BASDAI, and IBD patients with faecal calprotectin >100 µg/mg. Apart from these genera, no other taxa were shared between AS and IBD patients. CONCLUSIONS: In conclusion, the distinct gut microbiome of AS and AS-IBD patients compared to IBD patients and healthy controls is consistent with immunological and genetic evidence suggesting that the gut plays a different role in driving AS compared with IBD. However, enrichment of two potentially pathogenic genera in both diseases suggests that the presence of a shared/common microbial trigger of disease cannot be discounted.

Colorectal cancer guidelines seldom include the patient perspective.

OBJECTIVES: This study aimed to describe how colorectal practice guidelines (PGs) incorporate the patient perspective. STUDY DESIGN AND SETTING: We searched in the Guidelines International Network library, MEDLINE, National Guideline Clearinghouse, NHS Evidence database, and TRIP database. Two authors independently selected the PGs. We considered recommendations rated or worded as weak or conditional or suggesting multiple options, as potentially preference sensitive. Two authors independently evaluated if, in potentially sensitive recommendations, the patient perspective was incorporated. RESULTS: We included 28 PGs that contained 588 recommendations, being 256 potentially preference sensitive. Ten PGs (36%) included patients in the development process, and 12 (43%) provided information about patients' perspectives. Nine PGs (32%) included recommendations in which the patient perspective was explicitly considered, and 13 (46.4%) that recommended a discussion with the patient. From a total of 588 recommendations, 9.7% (25/256) of potentially preference-sensitive recommendations considered the patient perspective. The inclusion of patients in the development process was associated with a more frequent incorporation of the patient perspective in potentially preference sensitive recommendations (70% vs. 0%; P < 0.001). CONCLUSIONS: Guideline users should be aware that the incorporation of the patient perspective in colorectal cancer PGs is suboptimal. Guideline developers should make efforts to incorporate the patient perspective, especially in preference-sensitive recommendations.

Effects of combining simvastatin with rosiglitazone on inflammation, oxidant stress and ambulatory blood pressure in patients with the metabolic syndrome: the SIROCO study.

AIM: Individually, statins and thiazolidinediones (TZDs) show positive effects on atherosclerosis progression in cellular and animal models as well as patients with diabetes; however, their combined effects have not been studied. This study examines the effects of simvastatin combined with rosiglitazone on vascular inflammation, oxidant stress, ambulatory blood pressure (BP) and other atherosclerotic factors in patients with the metabolic syndrome. METHODS: This is a randomized, double blind, placebo-controlled study in 53 subjects with the metabolic syndrome. Participants were randomized to simvastatin 40 mg/day plus placebo vs. simvastatin 40 mg/day plus rosiglitazone 4 mg/day for 6 months. The primary endpoint was the between-group difference in high-sensitivity C-reactive protein (hs-CRP) and secondary variables including urinary isoprostanes, serum malondialdehyde (MDA), ambulatory BP, adiponectin, and lipid and glycaemic profiles. RESULTS: At study end, the group randomized to the simvastatin/rosiglitazone combination had a greater reduction in hs-CRP of 1.33 mg/dl, (p = 0.029) and showed a trend for a greater reduction in urinary isoprostane (-39%), (p = 0.056) compared to simvastatin/placebo group. Changes in MDA levels did not differed between groups (p = 0.81). 24-h systolic blood pressure (SBP) also showed a 4.5 mmHg reduction at 6 months (p = 0.06). Adiponectin levels increased by 3.91 µg/ml in the combination group over placebo, (p = 0.03) and blood glucose decreased in combination group vs. placebo. CONCLUSION: Our data show that patients with the metabolic syndrome given a statin/TZD combination manifest greater reductions in markers of vascular inflammation and oxidant stress, 24-h ambulatory BP and increases in adiponectin as well as improved glycaemic indices.

In vivo anti-hypertensive effect of Pterocarpus indicus aqueous leaf extract in male cats

This study aimed to investigate the anti-hypertensive potential of crude leaf extracts of Pterocarpus indicus (Narra). Hypertension was induced using Epinephrine HCI, 15-20 ug/kg body weight IV in 6 male cats, followed by an administration of Narra leaf extracts with a concentration of 0.25 g/kg BW IV at the peak of the epinephrines hypertensive effect. To test for the possible dose-response effect, the procedure was repeated using 0.5 and 1 g/kg BW IV Narra extracts. The systolic, diastolic and mean arterial blood pressures, pulse pressure, respiratory rate (SBP, OBP, MABP, PP and RR, respectively), respiratory and ECG (Q-R interval) amplitude, and the time for the Narra extract to effect were monitored using GrassO polygraph. Analysis of the data using General Linear Model (GLM) Repeated Measures showed that crude Narra leaf extracts at 0.25, 0.5 and 1 g/kg BW significantly lowered an epinephrine-induced rise in SBP (p=0.001), MABP (p=0.001), PP (p=0.0001) and ECG (Q-R interval) amplitude (p=0.05). However, there was no observed effect on the DBP (p=0.698), HR (p=0.9), RR (p=0.846) and respiratory amplitude (p=0.762). Moreover, no dose-response relationship was observed among the 3 doses of the narra extract on all physiologic parameters mentioned. Also, none of the doses was able to return the MABP to baseline (p=0.053). The observed decline in the SBP may have probably been due to the resultant decrease in the amplitude or force of contraction of the heart. Concomitantly, this may cause a decrease in the anti-hypertensive effect. (Author)

Limited volume resuscitation in penetrating thoracoabdominal trauma.

Trauma is the leading cause of death in young adults. Development of trauma centers in urban settings including emergency medical services has contributed greatly to the improved quality of trauma patient care. Based on animal experiments performed 3 decades ago, the traditional management of hypovolemic hemorrhagic shock includes adequate circulatory volume with aggressive initial infusion of crystalloid solution. However, in several recent animal studies, investigators have found that aggressive treatment with fluids before control of bleeding results in a higher mortality rate, especially if blood pressure is elevated. This notion has been supported by findings in a recent prospective, randomized study involving patients with penetrating injuries to the torso. This article discusses briefly the pathophysiology of shock and hemostasis and the current literature on fluid resuscitation, with emphasis on limited volume resuscitation in patients with penetrating thoracoabdominal injuries.

Interview with Dr. Evelyn Gacad. Fighting back with prevention and vigilance.

PIP: The National AIDS/STD Prevention and Control Program (NASCP) was created and implemented in the Philippines under the auspices of the Department of Health (DOH) in 1988 in response to increasing field reports about HIV-seropositive individuals. The NASCP grew out of a registry established to keep track of the reports and a committee created in 1986-87 to identify relevant issues. There was no government funding. Most funding therefore came from the World Health Organization. Other donors began contributing in 1990, paving the way for the NASCP's own budget from 1992. The program is now encouraging other government agencies to do their share in the fight against the spread of HIV. The struggle against AIDS requires sustained and continuous efforts. NASCP's current challenge is to make people understand that some policies can be counterproductive to the implementation of AIDS activities. For example, the DOH and the Philippine National AIDS Council argue against mandatory HIV testing. Fear of such testing within the target population is counterproductive to education campaigns. It is also unwise to focus activities upon the treatment of people infected with HIV. Since there are only a few HIV-infected people in the Philippines, it is more important to focus upon prevention to avoid future infection. The program manager discusses how changes in the DOH leadership affect the program and how the Church has been more openly hostile to some health secretaries than to others.^ieng

The National AIDS Council.

PIP: HIV infection was first documented in 1984 and although the AIDS epidemic remains in its early stages in the Philippines, leading epidemiologists estimate that by the year 2000, up to 100,000 Filipinos may be infected with HIV. On December 3, 1992, President Fidel Ramos signed Executive Order 39, creating the Philippine National AIDS Council (PNAC). The PNAC is a national advisory body which reviews and recommends policies on HIV/AIDS to the President and directs national approaches against HIV/AIDS domestically. The PNAC performs the following functions: advises the President and the Cabinet on matters concerning the prevention and control of HIV/AIDS; formulates and recommends appropriate plans, policies, programs, projects, and strategies for the prevention and control of HIV/AIDS; coordinates, monitors, and evaluates the implementation of the National AIDS/STD Prevention and Control Program; enlists other government agencies, nongovernmental organizations (NGO), private enterprises, professional groups, and other interested parties to respond to HIV/AIDS issues in order to ensure the best mobilization and use of resources; and facilitates the provision of technical, financial, and logistical support to government agencies and NGOs for the development and implementation of plans, programs, and projects to prevent and control HIV/AIDS. The government's strategy against HIV/AIDS and the institutional structure of the PNAC are described.^ieng

Electronic dental anesthesia versus topical anesthesia for the control of pain caused by nasopalatine block injections.

Topical anesthetics are routinely used to reduce the pain and discomfort that patients may experience during dental injections. Just recently, however, an anesthesia (Electronic Dental Anesthesia or EDA) which works by transcutaneous electrical nerve stimulation (TENS) was introduced to the dental profession. The purpose of this study was to determine whether an electrical signal as provided by an EDA is more effective than topical anesthesia in reducing pain and discomfort caused by local anesthetic injections. Two nasopalatine block injections, one using and EDA as the adjunct, and the other using a topical anesthetic ointment of Xylocaine 5% were performed on thirty-four patients. The volunteers were asked on the spot to report the level of the pain they felt during the penetration of the needle to the mucosa, during the deposition of local anesthetic solution, and their overall evaluation of the injections. The results of this investigation showed that the EDA is the more effective adjunct for local anesthetic injections compared to the traditional topical anesthetics.

Improving vaccination coverage in urban areas through a health communication campaign: the 1990 Philippine experience.

From March to September 1990 the Philippine Department of Health, with the assistance of the HEALTHCOM Project, carried out a national mass-media communication campaign to support routine vaccination services. The essential elements of the campaign strategy were as follows: focusing on measles as a way to get mothers to bring their children to the health centre; emphasizing logistic knowledge in the mass-media messages, in particular popularizing a single day of the week as "vaccination day" and giving clear information about the age for measles vaccination; and focusing on urban areas, which had lower vaccination rates than rural areas. Evaluation of the effects of the campaign indicates an increase in vaccination coverage and a substantial increase in the timeliness of vaccination that can be attributed to improvement in carers' knowledge about vaccination. Furthermore, most of the observed increase in knowledge was related to exposure to the mass-media campaign. There was no evidence of any programmatic change that could account for the increase in vaccination or evidence that increased health education efforts at health centres could account for the change in knowledge. These results indicate that when countries meet certain conditions--a high level of access to the media, sufficient expertise and funds available to develop and produce high-quality radio and television advertisements, and a routine system that is able to serve the increased demand--a mass communication campaign can significantly improve vaccination coverage.

PIP: The Philippine Department of Health conducted a national mass media communication campaign during the period March-September 1990 to support routine vaccination services. The campaign focused upon measles as a way to get mothers to bring their children to the health center, emphasized logistic knowledge in the mass-media messages, and focused upon urban areas with lower vaccination rates than rural areas. Examples of logistic emphasis include designating one day per week as vaccination day and giving clear information about the age for measles vaccination. An increase in vaccination coverage and a substantial increase in the timeliness of vaccination were observed which may be attributed to the improvement in carers' knowledge about vaccination. Most observed increase in knowledge was related to campaign exposure. There was no evidence of any programmatic change which could account for the increase in vaccination or evidence that increased health education efforts at health centers could account for the change in knowledge. These results indicate that when countries meet certain conditions, a mass communication campaign can significantly improve vaccination coverage. Conditions include access to media, expertise, and funds to produce and air high quality television and radio spots, and a routine system capable of handling the increased demand.

Update on fertility in the Philippines.

PIP: The 1986 Contraceptive Prevalence Survey provided an update on fertility in the Philippines. Among the major findings, it was noted that there was a decline on the national level in the number of births per 1000 population, and that overall total fertility rates, nationally and regionally, continued to decline, despite increases in several regions. Nationally, rural and urban age-specific fertility rates reflected a downward trend as well. However, rising age-specific fertility rates in most age groups were found in many rural regions. Cumulative fertility also remained high among women aged 40 to 49 years with around 6 children. Cumulative fertility among other age groups followed only a slight downward trend. Contraceptive prevalence increased between 1983 and 1986 regardless of the number of living children. Fertility differentials included age, maternal education, and occupational status.^ieng

Tropical fish medicine. Bacterial culture and evaluation of diseases of fish.

Bacteria are ubiquitous in nature. Fish are constantly exposed to bacteria, and usually only succumb to an infection after having been exposed to prolonged periods of stress. Before making a diagnosis of a bacterial disease, it is necessary to eliminate the possibility of environmental or parasitic problems. Environmental factors may act as stressors and can predispose a fish to bacterial disease while affecting the fish simultaneously. Clinical signs caused by the various bacterial pathogens are very similar. Therefore, to make a definitive bacterial diagnosis, it is necessary to culture and identify the organisms involved.

Family household and nuptiality changes: a search for some explanations from the recent past.

PIP: Using the demographic transition framework as a basis for analysis, the author examines the levels, trends, and differentials in household size and structure in the Philippines. Time-series data on average household size from the censuses show that the changes observed over time are closely associated with or have run parallel to the shifts in mortality and fertility. Data from the 1968, 1973, and 1983 National Demographic Surveys revealed small increases in 1-person households, modest increases in small-sized and moderate-sized households, and substantial decreases in large-sized households. The data also disclosed structural shifts among various types of family households. Between 1968 and 1983, family households experienced increasing nuclearization. While expectation for support in old age has somewhat diminished recently, parents' preference to join their daughters will have the effect of increasing the opportunity of females to head households. More highly educated persons exhibited a greater tendency to head the bigger-sized, extended family household, although this has diminished somewhat lately. Increases in the age at 1st marriage of both males and females affect the life span of family households, especially nuclear households. A multivariate analysis using macrolevel data as inputs demonstrated the very strong influences of the factors of desirability of marriage, availability of mate, and urbanization on the marriage pattern. Enhancing employment opportunities and creating appropriate mechanisms through which present incomes may be increased in the hinterlands under various rural development programs may help to diminish the values attached to children. The provision of more and better facilities for higher education especially in the disadvantaged provinces will enable young people, especially females, to gain access to higher learning, thus providing alternatives to early marriage and childbearing.^ieng

The value of children: the old people's view.

PIP: Personal interviews were conducted with 104 menopausal women and 205 grandparents from selected Laguna Lake (Philippines) area municipalities in an effort to study the benefits and cost of children from the viewpoints of grandparents and menopausal women and to investigate how such costs and benefits are related to the respondents' perceptions of family size and family formation. The data collected included age, sex, desired number and sex of children in the respondent's family, ideal age at marriage in years, reasons for ideal age at marriage for males, ideal birth interval, and number and age of children when problems were experienced. The following were included among the survey results: 1) children were valued as sources of inspiration and happiness and as eventual sources of economic assistance along with the feeling of accomplishment and satisfaction gained from watching the children grow and develop; 2) the disadvantages of having children fell under the categories of economic costs, emotional costs, and curtailment of freedoms; 3) the average desired family size of menopausal women was 4 children, and it was 5 children for grandparents; 4) the perceived ideal age at marriage of the respondents varied slightly; 5) an interval of 1-2 years between marriage and the birth of the 1st child was considered appropriate by 74% of the grandparents and by 63% of the menopausal women; and 6) economic costs of children and poor health were the primary reasons for the difficulties encountered by the respondents in raising their children.^ieng

The Filipino family in the year 2000.

PIP: Secondary sources of data from the National Demographic Surveys of 1968 and 1973 and National Censuses of 1903, 1939, 1948, 1960 and 1970 were used to present trends, patterns, and differentials in household size, structure and headship on the national and regional levels; changes in the stages of the family life cycle; trends in nuptiality during the 20th century on the national and regional levels; and nuptiality projections up to the year 2000. The analysis undertaken included means, percentages, ratios, projections, and comparisons of the results of the 2 surveys. Included among the results in terms of household size and structure, age composition of households, patterns and differentials in headship rates, life cycle of the family, and nuptiality were the following: 1) more than 1/2 of the households had 6 family members or more; 2) the most number of children occurred when the head of the family was between the ages of 24 and 44 years, when sex, urban-rural residence, and region were controlled; 3) an increasing trend in headship rates was exhibited by the single male and the widowed and divorced/separated female; 4) in 1973, the average interval between marriage and birth of the 1st child was 1.7 years; and 5) examination of past and recent regional nuptiality trends indicated a significant delay in age at marriage for females.^ieng