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Researchers are describing progress toward developing a new generation of chemotherapy agents that target and block uncontrolled DNA replication - a hallmark of cancer, viral infections, and other diseases - more effectively than current drugs in ways that may produce fewer side effects. Their article is scheduled for the Aug. 27 issue of ACS' Biochemistry, a weekly journal.

In the article, Anthony J. Berdis updates and reviews worldwide research efforts to develop drugs that target DNA polymerases, the enzymes responsible for assembling DNA from its component parts. Several promising strategies are already in use that inhibit uncontrolled DNA replication, particularly in anticancer therapy, but most produce severe side effects and are hampered by drug resistance, the researcher notes.

Berdis says that one of the more promising strategies to date involves the use of so-called nucleoside analogues, artificial pieces of DNA that inhibit replication by substituting for natural segments. Most nucleoside analogues directly target the active site of the polymerase enzyme, a non-specific approach that can also harm healthy cells which contain the enzyme. Berdis describes an alternative approach in which the drugs directly target damaged DNA while avoiding healthy DNA, side-stepping the polymerase enzymes of normal cells. The development, which shows promise in preliminary lab studies, could lead to improved nucleoside analogues with fewer side effects, he says. - MTS

In an effort to better understand how chronic stress affects the human body, researchers at the Yerkes National Primate Research Center and the Department of Psychiatry and Behavioral Sciences, Emory University, have created an animal model that shows how chronic stress affects behavior, physiology and reproduction.

Developing the animal model better positions the researchers to understand the neurohormonal causes of such stress and the body reaction in order to develop more effective treatment options for humans. The study is available in the current online edition of Molecular Psychiatry.

According to lead researcher Mark Wilson, PhD, chief of the Division of Psychobiology at Yerkes, "Chronic stress can lead to a number of behavioral changes and physical health problems, including anxiety, depression and infertility."

Via the animal model, the researchers found corticotropin releasing factor (CRF) is a key neurohormone involved in stress response. Wilson explains, "CRF is located in several different brain regions, serving different functions. Its release is important for our ability to adapt to every day stressors and to maintain our physical and emotional health."

In response to stress, CRF levels rise; CRF levels decrease when the stressor no longer is present. Chronic stress, however, increases the length and volume of expression of CRF in areas of the brain associated with fear and emotion, including the amygdala. Such chronic stress changes the body's response, and the resulting increased expression of CRF is thought to be the cause of such health-related stress problems including anxiety, depression and infertility.

To study the importance of CRF, the research team used a viral vector to increase the production of CRF in the amygdala of female rats.

"In our study, rats that continuously were exposed to CRF from this area of the brain experienced anxious and depressive behavior, decreased libido and disrupted ovarian cycles suggesting that persistent release of CRF such as occurs in chronic stress clearly affects multiple body systems," says Wilson. "These behavioral changes are similar to what we see in human females who are exposed to stressors on a daily basis."

Dr. Wilson and his research team next will attempt to learn more about the negative effects of increased CRF by examining actual molecular and cellular changes in specific brain areas targeted by the neurohormone. Knowing how CRF affects the brain positions the researchers to develop better treatment options.

Of the orphaned youth who are heading households in rural Rwanda can be classified as depressed, according to a report released on September 1, 2008 in Archives of Pediatrics & Adolescent Medicine, one of the JAMA/Archives journals.

Rwanda has one of the largest groups of orphans in the world, a result of the 1994 genocide and the epidemic of HIV infection. According to background information in the article, an estimated 290,000 orphans lived in the country in 2005. The authors note that these children are often placed in adverse conditions as a result: "Most African orphans have been absorbed into informal fostering systems," they say. "Such systems, however, are increasingly overwhelmed, and many orphans either head households or live on the street."

To investigate the effects of this change on the group, Neil W. Boris, M.D., of the Tulane University School of Medicine, New Orleans, and colleagues examined 539 Rwandan youths who were serving as the head of their households. A total 539 young people were evaluated, all younger than 24, with an average age of 20. The youth met with trained interviewers who administered scales that measured symptoms of grief, depression, adult support, and community marginalization, as well as surveys regarding demographics, health, vulnerable conditions, and risky behaviors.

In examining the data, the scientists found:
  • 77% of the youth population were performing subsistence farming.
  • 7% of the youth population had six or more years of schooling. 
  • In the status of their parents, 71.4% reported both parents dead, 26.2% reported one parent dead, and of these, almost 25% indicated that the genocide led to at least one of their deaths. s
  • 44% reported only eating one meal per day in the last week. 
  • 80% gave a health rating as poor or fair. 
  • The average depression scale score was higher than the standard cutoff score for adolescents. 53% of the subjects were positive in screening for depression. 
  • 76% agreed with a statement indicating that there is community rejection or orphans. 
  • 26% strongly agreed that they had at least one friend. 
  • 64% said they had lost their confidence in people. 
  • 40% agreed that life was meaningless or had lost faith in God since their parents' deaths.
The authors note some additional trends trends in this data. "Hunger, grief, few assets, poor health status and indices of social marginalization were associated with more depressive symptoms in this sample," they say. "Ten years after the Rwandan genocide and in the midst of the HIV/AIDS epidemic, the effects of poverty and social disruption on the most vulnerable youth in Rwanda are evident."

They state that further research is needed, examining the families that are supported by these youths. "The effect of caregiver depression on younger children living in youth-headed households is not yet known," they say. "Further study of orphans and vulnerable children in countries such as Rwanda, in particular, studies that inform large-scale interventions, are necessary if the next generation of youth is to thrive."

One of the few studies to look at the effects of religious participation on
the mental health of minorities suggests that for some of them, religion may
actually be contributing to adolescent depression.

Previous research has shown that teens who are active in religious services
are depressed less often because it provides these adolescents with social
support and a sense of belonging.

But new research has found that this does not hold true for all adolescents,
particularly for minorities and some females. The study found that white and
African-American adolescents generally had fewer symptoms of depressive at
high levels of religious participation. But for some Latino and
Asian-American adolescents, attending church more often was actually
affecting their mood in a negative way.

Asian-American adolescents who reported high levels of participation in
their church had the highest number of depressive symptoms among teens of
their race.

Likewise, Latino adolescents who were highly active in their church were
more depressed than their peers who went to church less often. Females of
all races and ethnic groups were also more likely to have symptoms of
depression than males overall.

Setting all other factors aside, the results suggest that participating in
religion at high levels may be detrimental to some teens because of the
tensions they face in balancing the conflicting ideals and customs of their
religion with those of mainstream culture, said Richard Petts, co-author of
the study, who did the work as a doctoral student in sociology at Ohio State
University.

"Most research has shown that religious participation, for the most part, is
good and can be very helpful for battling depression. But our research has
shown that this relationship does not hold true in all instances," he said.

While the study shows that females and males from certain groups may be more
inclined to become depressed, involvement in religious services still had an
overall positive affect for many youth in the study. The results do provide
important insight into the impact of religious participation on teenage
depression, but race and gender may only be part of the reason certain youth
were more depressed, Petts said.

"The study shows that we need to consider the broader social aspects of
institutions such as religion on an individual's well being, both good and
bad. We focus specifically on race and gender, but these are not the only
two factors that may be contributing to higher and lower depression among
youth," he said.

Petts, who is now an assistant professor of sociology at Ball State
University, conducted the study with Anne Jolliff when they were both
doctoral students at Ohio State. Jolliff is now a research coordinator at
Indiana University-Purdue University Indianapolis. The pair based the study
on data from the National Longitudinal Study of Adolescent Health, a study
surveying middle and high school students throughout the United States.

Adolescents in grades 7 through 12 were initially interviewed in school and
a random number of students were again interviewed at home. Students were
asked to identify the positive and negative feelings they had experienced in
the preceding week such as depression, loneliness, isolation, happiness, or
excitement. They were also asked about their behavior in the last year and
asked to identify their race, religious preference, and how often they
attended services during the same period of time.

Adolescents were then interviewed a second time one year later at home about
the same topics. Parents of these adolescents were also asked about their
child's moods and behaviors. Only the 12,155 adolescents who participated in
both parts of the study and had information from their parents were included
in this study.

The results were recently published in the journal *Review of Religious
Research.*

Among adolescents who never attended church, Asian-American adolescents
reported 4 percent fewer symptoms of depression in the preceding week than
did their African-American peers.

In comparison, Asian-American youth who attended church at least once a week
reported 20 to 27 percent more symptoms of depression than their white and
African-American peers who attended at the same level.

Latino adolescents fared about the same as Asian Americans, reporting 6 to
14 percent higher rates of depression symptoms than did African-American and
white teens when attending church at least once a week.

The results showed that in stark contrast to the findings for white and
African-American adolescents, Asian-American adolescents who never attended
services and Latinos attending at intermediate levels were the least likely
to be depressed within their groups.

The results suggest that something unique was affecting adolescents within
these two groups when they went to church often. Petts believes that the
traditional nature of religion for these two groups may be conflicting with
the ideals and customs of mainstream American society. This conflict may be
putting additional stress on these youth as they try to balance competing
principles and traditions, he said.

"Asian and Latino youth who are highly involved in a culturally distinct
church may have a more difficult time balancing the beliefs of their family
and their traditional culture with mainstream society. Their religious
institution is telling them what should be important in their lives and how
to behave, and mainstream society is saying something else," he said.

At higher levels of participation, Asian-American and Latino adolescents had
a harder time juggling which set of ideals to adopt because they were more
involved and committed to their religion.

Meanwhile, Asian-American adolescents who had lower levels of involvement in
church were able to focus more on life without worrying about conflicting
ideals, resulting in lower depression. At lower levels of involvement,
adolescents still gained the social support of their religious community
while also feeling in touch with mainstream society, Petts said.

The results also showed that the problem for Latino adolescents may be
two-fold. At high levels of involvement in their religious community, Latino
teens experienced the same tension between culture and society as some
Asian-American teens. This led to higher reports of depression symptoms
among these youth.

But Latino teens who never attended church reported high levels of
depression as well, reporting 26 to 28 percent higher rate of depression
symptoms than did white and African-American American youth. Religion is
often an important part of social support for these adolescents and no
involvement in their religion may leave these teens without a sense of
connection to their community and culture, he said.

"Participating to a certain extent may enable these youth to balance their
lives better. They have a connection with a religious community and all the
benefits it offers, but they are not so immersed that they're out of touch
with mainstream society. So they're sort of getting the best of both
worlds," Petts said.

The tension between society and religion may also help explain why females
who were sexually active report higher levels of depression than do sexually
active males. The disconnect between how their religion told them to act and
what they chose to do may cause these females to have higher emotional
distress and increased depression, he said.

In addition, Latina females who participated heavily in their religion were
more likely to become depressed then Latino males. Not only were these young
women more at risk for feeling depressed than were their male counterparts,
but they were also more depressed then Latina females who attended church at
intermittent levels.

"Females in these religious institutions often have subordinate status and
if females feel that they don't have equal say in that religious
institution, that may contribute to higher levels of depression," Petts
said.

This may also explain why attending church at intermediate levels resulted
in lower depression for these females. Latina females who attend at moderate
levels may benefit from the social support of the religious community, while
avoiding the patriarchal tensions experienced by those who attend services
weekly.

A new study shows that the innate immune system of humans is capable of
killing a fungus linked to airway inflammation, chronic rhinosinusitis and
bronchial asthma. Researchers at Mayo Clinic and the Virginia Bioinformatics
Institute (VBI) have revealed that eosinophils, a particular type of white
blood cell, exert a strong immune response against the environmental fungus
Alternaria alternata. The groundbreaking findings, which shed light on some
of the early events involved in the recognition of A. alternata by the human
immune system, were published recently in the Journal of Immunology.*

Eosinophils typically combat parasitic invaders of the human body larger
than bacteria or viruses, such as flukes or parasitic worms (collectively
known as helminths). Evidence from different experimental approaches
suggests that asthma and chronic sinusitis can arise when the body perceives
that it has encountered a disease-causing organism. Environmental fungi such
as Alternaria do not typically cause invasive infections like parasites but
for some reason, in certain people, the body responds as if it is being
attacked and chronic inflammation can result from the ensuing cascade of
immune-related events.

Principal Investigator Hirohito Kita, M.D., from Mayo Clinic, remarked: "Our
results strongly demonstrate that eosinophils have the capacity to recognize
and exert immunological responses to certain fungi such as Alternaria. We
have shown that CD11b receptors on the surface of eosinophils recognize and
adhere to beta-glucan, a major cell wall component of the fungus. This in
turn sets in motion the release of toxic granule proteins by the white blood
cells, leading to extensive damage and ultimate destruction of the fungus.
To the best of our knowledge, this is the first time that live eosinophils
and not just the intracellular components have been shown to target and
destroy a fungus."

The researchers used fluorescence microscopy to determine the outcome of the
interaction between eosinophils and A. alternata. The contact of fungus with
eosinophils resulted in bright red fluorescence due to the damaged fungal
cell wall and subsequent death of Alternaria. Immunohistochemistry confirmed
the release of toxic granular proteins by eosinophils due to contact with
the fungus.

Dr. Chris Lawrence, Associate Professor at VBI and the Department of
Biological Sciences at Virginia Tech, remarked: "T helper 2 (Th2) cells in
the immune system typically produce cytokine signaling molecules or
interleukins that lead to the recruitment of eosinophils for the
dysregulated immune response commonly associated with airway inflammatory
disorders. Continual exposure of sensitized individuals to common
environmental fungi like Alternaria may result in Th2 cells being constantly
activated to recruit eosinophils and this sustained defense mechanism
results in chronic inflammation. It has been shown previously that
degranulation of eosinophils causes damage of airway mucosa and enhances
inflammation. The next step in our transdisciplinary research collaboration
will be to use recombinant fungal proteins and fungal knockout mutants for
specific genes to dissect the different molecular steps involved in the
development and progression of this acute immune response."

Hirohito Kita added: "We have taken an important step in showing that the
innate immune system of eosinophils is capable of targeting an
asthma-associated fungus for destruction. The biological significance of
these results will need to be verified further in animal models and in
humans and our collaborative efforts with Dr. Lawrence's research group for
proteomics and functional genomics will be invaluable in this respect. We
suspect that the dysregulated immune responses to Alternaria, other
filamentous fungi, and perhaps chitin-encased insects, such as mites and
cockroaches, may play a pivotal role in chronic inflammation and the
subsequent development of bronchial airway disease."

The estimated rate of anaphylaxis in young women after human papillomavirus
(HPV) vaccination was significantly higher - 5 to 20 fold - than that
identified in comparable school-based vaccination programs, according to a
study published in *CMAJ* http://www.cmaj.ca/press/179_6_525.pdf. However,
the overall rates of anaphylaxis were low with no associated serious lasting
effects.

In a study of 114,000 women, a team of Australian researchers found 12
suspected of anaphylaxis, and confirmed 8 of these, in a 2007 vaccination
program in New South Wales, Australia. Symptoms included difficulty
breathing, nausea and rashes.

Dr. Julia Brotherton and colleagues postulate that reasons for an increased
rate of anaphylaxis may include possible allergic reaction to the vaccine
components, enhanced adverse event surveillance, higher rates of anaphylaxis
in women from midadolescence compared with men, and an apparent increase in
incidence of anaphylaxis in Australia.

The estimated rate of anaphylaxis following HPV vaccination was 2.6 per
100,000 doses administered compared with a rate 0.1 per 100 000 doses
administered in a 2003 school-based meningococcal C vaccination program.

HPV vaccination programs will begin this fall in the United Kingdom and
other European countries as well as in parts of Canada and the United
States.

Dr. Brotherton stresses "the importance of good training for staff
administering vaccines in school or other settings in the recognition and
management of suspected anaphylaxis and its reporting." They conclude that
anaphylaxis following the HPV vaccine is rare and vaccine programs should
continue.

Anaphylaxis is a rare but serious adverse event and highlights the
importance of vaccine safety studies after vaccine licensing and careful
management of reactions in immunization clinics, says Dr. Neal Halsey,
Institute of Vaccine Safety, Johns Hopkins Bloomberg School of Public Health
in a related commentary http://www.cmaj.ca/press/179_6_509.pdf. He states
"before concluding that the HPV vaccine is associated with higher rates of
anaphylaxis than other vaccines everywhere, cases in other populations
should be reviewed….As of July 21, 2008, 11 cases have been reported [in the
US] in 2008. Over 13 million doses of this vaccine have been distributed as
of the end of 2007."

A *CMAJ* editorial http://www.cmaj.ca/press/179_6_503.pdf states that this
study indicates the HPV vaccine is "remarkably safe." The study provides an
excellent opportunity for Canada's public health community "to restart
public discussions about the safety of the HPV vaccine, the precautions
taken to mitigate risks if anaphylaxis occurs, and the care taken in
surveillance for adverse events following vaccination," write Drs. Noni
MacDonald, Matthew Stanbrook and Paul Hebert.

Data from the largest randomized trial of its kind performed to date
indicate that the use of percutaneous coronary intervention (PCI) with the
CYPHER(R) Sirolimus-eluting Coronary Stent was comparable to bypass surgery
(coronary artery bypass grafting or CABG) in key safety endpoints in
patients with multi-vessel disease and diabetes. These data were presented
here recently at the European Society of Cardiology meeting.

The CYPHER(R) Stent is the only drug-eluting stent with such randomized
clinical data indicating that it is comparable to bypass surgery in these
key safety areas in patients with diabetes and multi-vessel disease, whose
coronary artery disease presents unique challenges.

Data from CARDia (Coronary Artery Revascularization in Diabetes Trial)
showed that after one year, there was no significant difference between PCI
with the CYPHER(R) Stent and bypass surgery in terms of death, heart attacks
or stroke, the primary endpoints for this study (10.1 percent for the
CYPHER(R) Stent compared to 10.2 percent for bypass surgery; p=0.98).

"The results of CARDia provide important new information to our
understanding of the treatment of patients with multi-vessel disease and
diabetes who present with coronary artery conditions," said Akhil Kapur,
M.D., London Chest Hospital, Barts and London National Health Service Trust,
London, UK, and one of the principal investigators.

"This is the largest randomized data set comparing angioplasty and surgery
in diabetic patients. The results of this study indicate that PCI with the
CYPHER(R) Stent was comparable to CABG in key safety outcomes in these high
risk patients." Aside from providing limited support for the CARDia trial,
Cordis Corporation has no financial relationship with Dr. Kapur and the
other principal investigators.

Key secondary endpoints, including revascularization (need for another
procedure), were remarkably low in both arms. As expected, patients who
received the CYPHER(R) Stent were somewhat more likely to undergo
revascularization (7.3 percent versus 2.0 percent; p=0.013). This
contributed to low but not statistically different rates of the composite
outcome of death, heart attack, stroke and repeat revascularization (15.1
percent for the CYPHER(R) Stent compared to 11 percent for bypass surgery;
p=0.217).

All patients in the study had diabetes and multi-vessel disease and were
amenable to either surgery or PCI.

The trial, conducted at 24 medical centers throughout the United Kingdom and
Ireland, was designed as a non-inferiority trial. In the discussion of the
trial in the hotline session, the CARDia investigators were congratulated on
the trial, but it was pointed out that due to enrollment of only 510 of the
originally planned 600 patients that there was insufficient power to answer
the specific question whether stenting was non-inferior to surgery in this
population.

*Overall Results Favorable for PCI (the CYPHER(R) Stent or a Bare Metal Stent)
*

The CYPHER(R) Stent portion of this study was part of an overall comparison of
PCI versus surgery. The CARDia trial included 510 patients randomized to
receive bypass surgery (254 patients) or PCI with either the CYPHER(R) Stent
or a bare metal stent (256 patients). Of those patients who received PCI,
180 patients (71%) were randomized to receive the CYPHER(R) Stent and 72 were
randomized to receive a bare metal stent. The CYPHER(R) Stent cohort was
uniformly numerically lower for all outcomes compared to the overall PCI
population.

The composite rate of death, heart attack and stroke at one year was similar
between the two groups (11.6 percent for PCI and 10.2 percent for surgery;
p=0.63). Specifically, the rates of death for total PCI was 3.2 percent
compared to 3.3 percent for bypass surgery (p=0.83) and clinically reported
non-fatal heart attacks was 8.4 percent for PCI compared to 5.7 percent for
bypass surgery (p=0.25). The rate of stroke showed a trend toward being
lower with PCI (0.4 percent) compared to bypass surgery (2.5 percent,
p=0.09).

*Trial Results Show Benefits of PCI to Bypass Surgery for Patients *

For many years, patients with multi-vessel disease and diabetes were treated
with coronary bypass surgery, considered to be the gold standard for these
difficult-to-treat conditions. However, surgery is associated with higher
health care costs as well as a lengthy recovery period. Patients receiving
PCI are treated with minimally invasive techniques that greatly reduce both
health care costs, as well as the amount of time it takes a patient to
recover and resume activities of daily living.

"Prior to this trial, there were limited randomized clinical data directly
comparing the CYPHER(R) Stent to bypass surgery in diabetics so these results
are critical to our understanding of how to optimally treat coronary artery
disease in patients with diabetes," said Campbell Rogers, M.D., Chief
Technology Officer, Cordis Corporation. "These results are also important
because the CYPHER(R) Stent is now the only drug-eluting stent with randomized
clinical data compared to bypass surgery specifically in this
difficult-to-treat patient population."

The study was supported by major grants from the Hammersmith Hospitals
special trustees, Eli Lilly Corporation, Sanofi Aventis and Cordis
Corporation. Further support was provided by Boston Scientific, Medtronic,
Guidant and Jomed.

*Data Consistent with other Trials of the CYPHER(R) Stent in Patients with
Diabetes*

The use of drug-eluting stents in patients with diabetes has been the focus
of debate and discussion within the medical community for some time. The
data from CARDia are consistent with other clinical trial data on the use of
the CYPHER(R) Stent in patients with diabetes.

According to data appearing recently in the *Journal of the American College
of Cardiology*, in patients with diabetes, the CYPHER(R) Stent outperformed
the Taxus(R) Stent with significantly lower rates of in-segment restenosis (a
reblockage within the stented area), target lesion revascularization (TLR;
the need for another interventional procedure) and major adverse events
(MACE, a composite of death, heart attack and TLR) at nine months.

In this multi-center randomized clinical trial, the six month rate of
in-segment restenosis was more than five times lower for the CYPHER(R) Stent
compared to the Taxus(R) Stent (4.0 percent vs. 20.8 percent respectively (p <
0.001). Most important for patients and physicians, key clinical outcomes
measures were about four times lower for the CYPHER(R) Stent -- at
nine-months, clinically driven TLR for the CYPHER(R) Stent was 1.5 percent
compared to 6.0 percent for the Taxus(R) Stent (p=0.032) while the composite
clinical endpoint of MACE was 2.0 percent for the CYPHER(R) Stent compared to
8.0 percent for the Taxus(R) Stent (p=0.010).

The CYPHER(R) Stent does not have an approved indication for use in patients
with diabetes or multi-vessel disease in the United States.

*About the CYPHER(R) Stent *

The CYPHER(R) Stent has been chosen by cardiologists worldwide to treat
approximately three million patients with coronary artery disease. The
safety and efficacy of the device is supported by a robust clinical trial
program that includes more than 70 studies that examine the performance of
the CYPHER(R) Stent in a broad range of patients.

Nerve-sparing radical prostatectomy (NSRP) is the gold-standard therapy for
prostate cancer in men with a life expectancy of 10 years or more. The risk
of erectile dysfunction (ED) following NSRP is significant. This is caused
by neuropraxia - the usually temporary failure of nerve conduction in the
absence of structural changes due to compression, ischemia or blunt injury -
which inevitably occurs during the procedure. Ultimately this may lead to
the development of fibrosis within the corpus cavernosa and cause ED.

To prevent the onset of postoperative ED, the use of phosphodiesterase type
5 (PDE5) inhibitors was introduced. These agents prevent the breakdown of
cyclic guanosine monophosphate in cavernosal tissue, which plays a role in
the prevention of cell death and fibrosis, and may thus exert a protective
effect on cavernosal smooth muscle.

Participants were recruited to this first robustly designed, evidence-based,
multi-centre study approximately one month before they were scheduled to
undergo NSRP. A total of 423 patients completed the study. The inclusion of
the on-demand dosing regimen enabled comparison of the currently recommended
guidelines for the use of PDE5 inhibitors with a proposed nightly dosing
regimen, which was suggested to have potential positive effects on erectile
function. The results clearly show that nightly dosing with vardenafil does
not have any effect beyond that of on-demand use.

The study shows that on-demand use of vardenafil during the treatment period
was associated with significantly greater erectile function and sexual
intercourse completion rates compared to placebo. The success rates for the
vardenafil on-demand group were also higher than for the nightly group.
These data indicate that the use of on-demand vardenafil is of greater
benefit than nightly treatment in patients following NSRP surgery and, in
general, support the on-demand use of PDE5 inhibitors following NSRP surgery
over a daily dosing regimen. This prompts reconsideration of the current
practice of prescribing nightly PDE5 inhibitor therapy, as on-demand use of
vardenafil is equally effective in men with ED following NSRP, a notoriously
difficult-to-treat patient population.

Nearly twenty percent of 14 year-olds say they've been drunk at least once,
according to the U.S. Surgeon General, and recent news points out dangers of
alcohol use by the young:

- The Partnership for a Drug-Free America released a study in August,
2008 of 6,500 teens in which 73% said school stress caused them to drink and
take drugs.

- A Columbia University study, also released in August, found that
"problem parents," those who let their kids stay out past 10:00 p.m. on
school nights in particular, are putting them in situations where they are
at risk for drinking and drug use.

- About 100 university leaders called for a national discussion of
lowering the drinking age back to 18, saying it's not clear that 21 works.

The middle school years are crucial in the battle to prevent early alcohol
use. Young adolescents' bodies and friendships are changing. They start
pulling away from parents; yet seek out other adults for guidance. It's the
most vulnerable time, specialists say, but also one of the last times they
still can be influenced by adults.

No one sets out to be a disengaged parent. But it's hard to be vigilant and
talk to your kids about complicated topics when you are constantly on the
go. "As parents better understand the physiological effects of alcohol on
the body and the fact that their children might be starting younger, it can
motivate them to have this sometimes awkward conversation," says Shirley
Malcom, head of the Education and Human Resources office at AAAS. "That's
where the science can help."

Members of The Science Inside Alcohol Project at AAAS are writing a book for
middle school parents and developing an interactive Web-based science and
health curriculum explaining how alcohol affects adolescents' brains and
bodies. Based on extensive research, the AAAS team suggests five steps
parents can take to talk with their kids about alcohol.

1. Find Teachable Moments -- We live in a culture of celebrity. If a
celebrity your child admires admits to a drinking problem, or an instance of
alcohol abuse occurs in your community, talk about it. Ask your middle
school student if she knows anyone who drinks alcohol and whether it is at
parties or has been brought into her school. Answer questions. Have this
conversation often.

2. Talk to Your Kids When Everything is Fine -- Middle school students
are volatile, hormonal beings. They are sweet and wonderful one moment, and
blow up the next. Pick a time when things are quiet and they're a captive
audience such as in the backseat of your car. Don't take no for an answer.

3. Engage Your Kids in the Science of Alcohol -- Adolescents are
incredibly self-involved. Alcohol can cause memory loss, impair sports
performance, incite embarrassing behavior and affect how they feel and look.
Make them aware of these facts. If there is a history of alcoholism in your
family, explain about genetic predispositions towards alcohol abuse.

4. Be Vigilant -- There's no alternative to monitoring your kids. Have an
early curfew. Know where they are at all times. Even if you are not home on
a weeknight, make sure you can reach your kids by phone. Get to know their
new friends and their parents. Find out what their rules and level of
engagement are.

5. Learn to Trust Your Child -- Now's the time when all the work you've
put into creating a value system for your child begins to pay off. Set
limits and enforce rules, but remember to give your child room to make his
or her decisions, within your comfort zone. Praise them when they do well.
It's worth a thousand words.

For women with chronic kidney disease (CKD), getting pregnant is very rare,
and a successful pregnancy is even more uncommon, especially for women on
dialysis.

In the July-August 2008 issue of *Nephrology Nursing Journal,* Mary Coyle
and co-authors present a case report of a 35-year-old woman with Stage 5 CKD
who successfully completed a 39-week pregnancy while on hemodialysis. The
pregnancy was diagnosed at seven weeks, and five three-hour hemodialysis
sessions per week were started right away, say the authors.

A care team was assigned to the patient and her family, which included a
nephrologist, a dialysis center nurse practitioner, a nurse manager, a
dietician, a social worker, and a core group of nurses who would dialyze
her. This group, say the authors, was crucial in monitoring signs and
symptoms and maintaining a continuum of care. The care team used
recommendations in the available literature to manage blood urea nitrogen
levels, fluid removal by ultrafiltration and other issues.

The nurse practitioner also shared status updates with the perinatologist
and perinatal center nurse practitioner throughout the pregnancy. The
perinatologist saw the patient every two weeks and with greater frequency
when she reached 24 weeks.

The patient's anemia worsened during the pregnancy, and she also developed
hypertension, pre-eclampsia and polyhydramnios, all common among women on
dialysis. Despite these complications, fetal heart rate testing and OB
ultrasounds revealed an active, growing fetus. A scheduled cesarean section
took place at 39 weeks, and the patient delivered a five-pound, seven-ounce
daughter. Mother and baby were discharged after five days.

Coyle and co-authors say that they were fortunate their patient was highly
motivated and committed to following treatment guidelines. While limited
data currently exist, more extensive research is needed to determine
appropriate guidelines, better understanding of risks and clear indications
of how medications and treatments affect the fetus.

*"A Successful 39-Week Pregnancy on Hemodialysis: A Case Report."* Mary
Coyle, MS, FNP; Elyn Sulger, BSN, RN, CNN, CAN-BC, CPHQ, LNC; Cindy
Fletcher, MSW, LMSW; and Diane Rouse, MS, RD, CDN *Nephrology Nursing
Journal*; July-August 2008; http://www.annanurse.org/journal

*Nephrology Nursing Journal *is a refereed clinical and scientific resource
that provides current information on a wide variety of subjects to
facilitate the practice of professional nephrology nursing. Its purpose is
to disseminate information on the latest advances in research, practice, and
education to nephrology nurses to positively influence the quality of care
they provide.

Alaska Gov. Sarah Palin (R) on Wednesday accepted the vice presidential
nomination for the Republican Party at the party's national convention in
St. Paul, Minn., the AP/Washington
Post<http://www.washingtonpost.com/wp-dyn/content/article/2008/09/03/AR2008090300488.html>reports
(Espo, AP/Washington
Post, 9/4). Several print publications recently reported on the reaction to
the nomination, as well as the announcement that her 17-year-old daughter,
Bristol, is pregnant. Summaries appear below.

~ ABC News <http://abcnews.go.com/Health/story?id=5711359&page=1>: ABC
Newsexamined how the announcement of Bristol Palin's pregnancy has
"reignited"
debate over whether abstinence-only education programs, which Palin
supports, are effective in curbing teenage pregnancies. According to ABC
News, sexual health experts "overwhelmingly" agree that comprehensive sex
education programs are a more effective strategy in reducing teen births
than abstinence-only programs (Childs, ABC News, 9/3).

~ Miami Herald<http://www.miamiherald.com/news/top-stories/story/671263.html>:
The Herald examined views of teen pregnancy among South Florida teens, of
whom 7,000 become pregnant annually, as well as parents in the region.
According to the Herald, the presence of teen pregnancy in the news has
provided an opportunity for parents to discuss sex and pregnancy with their
children (Kaleem, Miami Herald, 9/4).

~ New York Daily News: The "unwed pregnancy" of Bristol Palin "has been
spun" by Republican presidential candidate Sen. John McCain's (Ariz.)
"message-managers as an example of strong family values," the Daily
Newsreports. According to the Daily
News, the "muted, nonjudgmental" reaction of social conservative leaders
lies in contrast to conservatives' praise of former Vice President Dan
Quayle's (R) criticism in 1992 of the show "Murphy Brown," in which the
title character had a child out of wedlock (DeFrank, New York Daily News,
9/4).

~ New York Times<http://www.nytimes.com/2008/09/04/fashion/04marriage.html?partner=rssnyt&emc=rss>:
Reporting on Bristol's plans to marry the father of her child, the
Timescites studies that show teenage marriages today are two to three
times more
likely to end in divorce than marriages between people ages 25 or older.
According to the Times, even some experts who "acknowledge that teenage
marriage is a risky proposition" said that marriage is a "healthier choice"
for the pregnant woman than single motherhood (Kershaw, New York Times,
9/4).

~ Philadelphia Inquirer<http://www.philly.com/inquirer/magazine/20080904_Teen_pregnancy_s_new_twist.html>:
The Inquirer examines whether the public's perception of teen pregnancy has
changed in light of Palin's daughter's pregnancy and other recent
high-profile teen pregnancies (Pompilio, Philadelphia Inquirer, 9/4).

~ Pittsburgh Post-Gazette<http://www.post-gazette.com/pg/08247/908943-470.stm>:
The "'Mommy Wars' -- the seemingly endless debate over whether mothers
should work or stay home with their kids" -- has "erupted" over the choice
of Palin as McCain's running mate, the Post-Gazette reports. According to
the Post-Gazette, many women can relate to Palin's situation, considering
that the most recent government statistics available show that nearly
two-thirds of mothers in the country with preschool-age children were in the
work force in 2003 (Carpenter, Pittsburgh Post-Gazette, 9/3).

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