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From the Townsend Letter
December 2015

briefed by Jule Klotter
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Circumcision, HIV, and STDs
Circumcision studies conducted on adult HIV-free African men show that removing the foreskin lessens the likelihood of their acquiring HIV from sexual partners. Circumcision, however, does not prevent the men from transmitting HIV to their partners. Although the exact reasons for this one-sided protection is unknown, researchers speculate that the foreskin's epithelial surface and microbiota may be involved.
Lance B. Price and colleagues found that the composition of penile microbiotas (collected at the junction between the shaft and glans) in 12 HIV-negative Ugandan men changed significantly after circumcision. Pre-circumcision samples were more heterogeneous with more anaerobic bacteria. The researchers suggest that anaerobic bacteria may stimulate genital mucosal inflammation and increase Langerhans cells' susceptibility to HIV infection. The foreskin's inner surface contains large numbers of Langerhans cells, a preferred target for HIV. Interestingly, circumcision has no effect on the prevention of other sexually transmitted disease rates, according to studies investigating Treponema pallidum (syphilis), Neisseria gonorrhoeae, Trichomonas vaginalis, or Chlamydia trachomatis (Dinh et al).
The HIV-transmission studies of adult men in developing nations provide rationale for circumcision in adults, but should these studies be applied to male infants in developed countries? Unlike in adults, the neuron-rich foreskin in babies is typically fused to the glans penis; it does not retract. No one has studied the long-term physiological or psychological effects of cutting off an infant's foreskin. The Royal Dutch Medical Association, the British Medical Association, the Canadian Paediatric Society, and the Royal Australasian College of Physicians do not recommend routine circumcision in healthy infant boys, according to Angelika F. Na and colleagues. The Royal Dutch Medical Association views infant circumcision as "'a violation of children's rights to autonomy and physical integrity.'" The other countries say that there isn't enough consistent evidence of benefit to offset the risks of surgical complications and the medical cost.
The American Academy of Pediatrics 2012 policy statement does not recommend routine circumcision but does list prevention of urinary tract infections and HIV and STD prevention as benefits of infant circumcision. Na and colleagues point out that most UTIs occur in boys with underlying renal tract abnormalities and that UTIs respond to antibiotic treatment. They question the benefits of circumcising babies when most boys are not at risk for a treatable infection. As for HIV and STD prevention, no studies support a link between infant circumcision and HIV/STD prevention. Condoms, not circumcision, are the most effective way to prevent STDs.

Dinh MH, Fahrback KM, Hope TJ. The role of the foreskin in male circumcision: an evidence-based review. Am J Reprod Immunol. March 2011;65(3):279–283. Available at Accessed October 3, 2015.
Dinneen EP, Bunker CB, Dinneen MD. Male circumcision – when is it justified? Trends Urol Mens Health. May/June 2013;22–25. Available at Accessed October 3, 2015.
Na AF, Tanny SPT, Hutson JM. Circumcision: Is it worth it for 21st-century Australian boys? J Paediatr Child Health. 2015;51:580–583. Available at Accessed October 3, 2015.
Price LB, Liu CM, Johnson KE, et al. The effects of circumcision on the penis microbiome. PLoS ONE. January 2010;5(1):e8422. Available at Accessed October 3, 2015.

Benign Prostatic Hyperplasia, Nocturia, and Physical Activity
Standing more and sitting less may prevent benign prostate hyperplasia (BPH), according to a 2014 South Korean study. BPH is characterized by lower urinary tract symptoms such as increased frequency, increased urgency, a feeling of incomplete bladder emptying, and nocturia (excessive urination at night). Eight of 11 studies have found an inverse relationship between physical activity and BPH, according to Ho Won Lee and colleagues. In order to identify beneficial aspects of physical activity, the authors looked at frequency of exercise, exercise time, sedentary time, and nonsedentary time (e.g. light field work, washing windows, slow cycling) in 582 men, age 40 and older, without prostate cancer.
Unlike other studies, the Korean study found that high-intensity and longer-duration exercise does not reduce the risk of BPH (defined as ≥ 25mL of prostate volume and an International Prostate Symptom Score [IPSS] of ≥8). In fact, men who engaged in sweat-producing exercise 5 or more times per week had an overall higher BPH risk (OR, 1.26; 95% CI, 0.68–2.33). However, sedentary time showed a significant linear relationship with BPH and with prostate volume: "Subjects with lower levels of sedentary time (4.5-7.0 hr/day) had a significantly lower risk of BPH (OR, 0.93; 95% CI, 0.52-1.67) than those with a higher sedentary time (>7 hr/day) (OR, 1.72; 95% CI, 0.96-3.09) (P for trend=0.05)." Clinical trials are needed to confirm the relationship between sedentary behavior and BPH.
Although physical activity did not prevent BPH in the South Korean study, epidemiological evidence from a 2015 study indicates that activity might alleviate nocturia in some men. "Nocturia increases with age and is estimated to occur in over 50% of men over the age of 45 (regardless of BPH status)," say Kathleen Y. Wolin and colleagues. Excessive urination at night is associated with poor sleep and depression. Wolin and colleagues analyzed data from the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial, an ongoing clinical study that is investigating the effects of cancer screening on cancer-specific mortality. The trial enrolled 76,705 men, aged 55 to 74, with no reported history of prostate cancer. Wolin and colleagues used data from the intervention arm of the study; these men completed questionnaires on lifestyle, BPH-related outcomes, and nocturia at baseline (c.1993) and an additional questionnaire on BPH, nocturia, and physical activity over 10 years later (2006–2008). The researchers found a weak association between physical activity and BPH but a strong inverse association between physical activity and nocturia. Nocturia was defined as waking 2 or more times a night to urinate. Men whose only complaint was nocturia showed a stronger correlation. The association between physical activity and nocturia was statistically nonsignificant for men with a BPH diagnosis, elevated PSA, or large prostate volume. As with the Korean study, the results of this study also need to be tested in a clinical trial.

Lee HW, Kim SA, Nam JW, Kim MK, Choi BY, Moon HS. The study about physical activity for subjects with prevention of benign prostate hyperplasia. Int Neurourol J. 2014;18(1):155–162. Available at Accessed September 18, 2015.
Wolin KY, Grubb RL, III, Pakpahan R, et al. Physical activity and benign prostatic hyperplasia-related outcomes and nocturia. Med Sci Sports Exerc. March 2015;47(3):581–592. Available at Accessed September 18, 2015.

Rapamycin, an Anti-Aging Drug?
Rapamycin, an antifungal, anticancer, and immune-suppressing compound secreted by the bacterium Streptomyces hygroscopicus, is the basis for an anti-aging drug being developed by the Swiss pharmaceutical company Novartis. Animal research has shown that rapamycin delays the onset of several age-related conditions, including cancer, heart disease, bone loss, and Alzheimer's disease. It has also reversed cardiac aging and Alzheimer's. FDA approved rapamycin as a drug for transplant patients to help prevent organ rejection in 1999. Since then, patentable rapamycin derivatives have been FDA-approved to inhibit some kidney, lung, and breast cancers. Independent of its effects on disease conditions, rapamycin has lengthened lifespan in mice who began receiving the drug at 20 months (late middle age).
Rapamycin inhibits a cellular pathway that regulates growth and metabolism. This pathway, called TOR (target of rapamycin), works like a factory's circuit breaker, says science writer Bill Gifford: "When it's activated, the cell grows and divides, consuming nutrients and producing proteins. When mTOR [mammalian TOR] is turned down, the 'factory' switches into more of a conservation mode, as the cell cleans house and recycles old proteins. …" This housecleaning phase has been linked to longer lifespans. When Roman V. Kondratov and Anna A. Kondratova gave rapamycin to mice genetically predisposed to premature aging, mTORC1 (which suppresses mTOR signaling) greatly increased and the mice lived 8 to 12 months longer than controls. Matt Kaeberlein and Daniel Promislow at the University of Washington plan to test rapamycin's ability to prevent age-related arterial stiffness and cardiac decline in middle-aged pet dogs.
Despite its anti-aging effects, scientists and physicians question rapamycin's use in older people because of its immune-suppressing properties. Rapamycin is known to impair wound healing. A 2014 study indicates that rapamycin may modulate rather than suppress immune activity. In this study, low doses of everolimus, a rapamycin derivative, increased antibody response to a flu vaccine in people 65 and older. However, vaccine response does not necessarily reflect the body's response to an actual infection, according to Janko Nikolich-Zugich, chair of the department of immunobiology at the University of Arizona and codirector of the Arizona Center on Aging.
At this point, too many questions about rapamycin's safety, dosage, and timing remain to use it as an anti-aging drug in healthy middle-aged people. Novartis spokesperson Mariellen Gallagher told Gifford: "‘It is far too early to tell whether low-dose rapamycin will lengthen human life span. A favorable risk/benefit ratio needs to be demonstrated in clinic trials to be sure that mTOR inhibitors such as rapamycin have acceptable safety and efficacy in aging-related conditions in humans.'"

Bushak L. An anti-aging drug in the works? First steps toward boosting immune system, delaying aging [online article]. Medical Daily. December 27, 2014. Accessed September 24, 2015.
Gifford B. Inside Novartis's push to produce the first legitimate anti-aging drug [online article]. February 12, 2015. Accessed September 24. 2015.
Kondratov RV, Kondratova AA. Rapamycin in preventive (very low) doses. Aging. March 2014;6(3):158–159. Available at Accessed September 26, 2015.

Service Dogs for Vets with PTSD
Although the US Veterans Affairs Department funds service dogs for physically disabled soldiers, the agency has not yet approved their use for soldiers with posttraumatic stress disorder (PTSD) or traumatic brain injury (TBI). The agency is awaiting results from clinical trials that assess the effect of a service dog on a combat veteran with PTSD or TBI. Service dogs perform a variety of tasks for physically disabled veterans such as picking up and retrieving objects and opening doors. Service dogs can also provide active support for those with PTSD, such as waking their human partners from a nightmare. Perhaps most importantly, service dogs provide emotional support. Marguerite O'Haire at Purdue University's College of Veterinary Medicine is leading a placebo-controlled study involving 100 post-9/11 veterans, according to an article in Military Times. The researchers will be looking at service dogs' effects on medical symptoms, medication use, social anxiety, relationships, stress levels, and other factors. Meanwhile, a novel program at several veterans' medical facilities shows that, by training service dogs, veterans with PTSD can retrain themselves.
The Warrior Canine Connection (WCC) uses veterans with PTSD and TBI to train service dogs for soldiers with spinal cord injuries. This nonprofit organization has WCC programs at Walter Reed National Military Medical Center, Fort Belvoir, National Intrepid Center of Excellence, and the Palo Alto Veterans Administration Healthcare System. "WCC's training philosophy is based on positive methods of shaping behaviors and the premise that mastering the skills and patience required to train a service dog helps the WCC trainers regain control of their own emotions, focus their attention, and improve their social competence and overall sense of well-being," according to an article in Psychiatric Annals. Social worker and service dog trainer Rick Yount developed the program.
The mission of helping another disabled veteran, by providing a well-trained, valuable service dog free of charge, motivates trainer-veterans to surmount their own problems. These dogs are bred to be highly attuned to people's emotional affect, so their trainers must maintain confidence and a positive attitude. Trainers use praise and treats to teach the dogs that "the world is a safe place." Program participants have reported that the patience and positive techniques used in dog training have been highly useful in their interactions with their own children. Dogs in the training program are exposed to a wide variety of environments and experiences, requiring their trainers to move out into the community. Trainers also need to stay in the present moment in order to take advantage of "teachable moments." A veteran, triggered into remembering past traumas, cannot convince a startled dog that a backfiring car is not a threat. In addition to increased patience, emotional regulation, and impulse control, program participants report improved sleep, decreased depression, decreased use of pain medications, increased sense of belonging/acceptance, improved family dynamics, lower stress levels, and increased sense of calm.
The WCC program brings new meaning to the healing power of animal-assisted therapy.
Kime P. New studies focus on service dogs and PTSD. Military Times. May 10, 2015. Available at Accessed September 23, 2015.
Yount RA, Olmert MD, Lee MR. Service dog training program for treatment of posttraumatic stress in service members. United States Army Medical Department Journal. April–June 2012;63–69. Available at Accessed September 23, 2015.
Yount R, Ritchie EC, St. Laurent M, Chumley P, Olmert MD. The role of service dog training in the treatment of combat-related PTSD. Psychiatr Ann. June 2013;43(6):292–295. Available at EBSCO Host. Accessed September 23, 2015.

Successful Aging
Successful aging entails more than freedom from disability and disease, according to Dilip V. Jeste, MD, and colleagues. Jeste et al.conducted a study to test the hypothesis that "older age would be associated with worse physical and cognitive functioning and lower [self-rated successful aging] SRSA scores." To their surprise, older age did not correlate with lower scores. "Perfect physical health is neither necessary nor sufficient for successful aging as defined by the older adults themselves," they state. Resilience and freedom from depression, however, are.
Their 2014 SAGE (Successful Aging Evaluation) study recruited 200 people in their 50s, 200 in their 60s, 250 in their 70s, 411 in their 80s, and 238 in their 90s. (Initially, they sought 325 participants for the 9th and 10th decades but could not get that many people in their 90s, so they added more in their 80s.) None of the participants required daily skilled nursing care, had a prior diagnosis of dementia, or had a terminal illness. The researchers questioned participants about their demographics, general health, depression and anxiety, and cognitive function in a structured 25-minute phone interview. A follow-up mail-in survey consisted of validated questionnaires to further assess physical and mental functioning, self-perceived cognitive deficits, depression, positive psychological factors (e.g., optimism), and self-rated successful aging. A total of 1006 out of 1300 participants completed the survey.
"Contrary to our hypothesis, older age was associated with higher SRSA, despite worse physical and cognitive functioning," say Jeste and colleagues. "… Possible explanations for this paradoxical result include acceptance of physical limitations, contentedness with overall accomplishments in life, a more realistic appraisal of one's own strengths and limitations, reduced preoccupation with social comparison (peer pressure), and greater emotional stability." The researchers noted an interesting correlation between physical function and depression: the SRSA scores of people with poor physical function (lowest tertile) and no or minimal depression were comparable to scores belonging to physically healthy people with moderate to severe depression. Similarly, SRSA scores of physically impaired people with high resilience scores were comparable to scores belonging to physically healthy people with low resilience. Resilience is the ability to cope with stress and adapt to change, such as the change in function and life circumstances that come with aging.
The study's results indicate that greater resilience, lower depression, better physical health, and older age are primary factors associated with successful aging. However, more research is needed to determine whether increasing resilience or reducing depression actually produces more positive SRSA scores. Although the SAGE study does not show causal relationships, it does challenge negative attitudes about aging. Instead of focusing solely on physical and mental functioning, clinicians can recognize that resilience, a sense of purpose, and other psychological factors may be equally important in successful aging. Clinicians can also use SRSA scores to measure outcomes.

Aldwin CM, Igarashi H. An ecological model of resilience in late life. Ann Rev Gerontol Geriatr. January 2012. Available at Accessed September 24, 2015.
Jeste DV, Sayla GN, Thompson WK, et al. Older age is associated with more successful aging: role of resilience and depression. Am J Psychiatry. Feb.1, 2013;170(2):188–196. Available at Accessed September 24, 2015.

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