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Should Genital Hiatus/Perineal Body Be Measured at Rest or on Valsalva?

Ow LL, Subramaniam N, Kamisan Atan I, Friedman T, Martin A, Dietz HP

Female Pelvic Med Reconstr Surg, 2018 7 7;25(6):415-418.
PMID: 29979358 DOI: 10.1097/SPV.0000000000000608

OBJECTIVE: Genital hiatus (Gh) and perineal body (Pb) are part of the Pelvic Organ Prolapse Quantification assessment system, but it is unclear whether measurements should be taken at rest or on Valsalva. This study was designed to assess the predictive value of Gh and Pb measurements obtained at rest and on Valsalva for signs and symptoms of pelvic organ prolapse (POP).
METHODS: This is a retrospective study involving 416 women who presented to a tertiary urogynecology unit with symptoms of pelvic floor dysfunction. Genital hiatus and Pb were measured at rest and on maximal Valsalva. The strength of association between binary markers of POP and measurements of Gh/Pb was estimated using logistic regression analysis. Receiver operator characteristic statistics were used to compare predictive values of Gh and Pb measurements obtained at rest and on Valsalva.
RESULTS: A total of 451 women were seen during the study period. Thirty-five were excluded owing to missing data, leaving 416. Fifty-four percent (n = 223) complained of POP symptoms. On examination, 80% (n = 332) had significant POP (stage 2+ in anterior or posterior compartments or stage 1+ in the central compartment). On imaging, significant POP was diagnosed in 66% (n = 275). Mean hiatal area was 22 cm (SD, 7; range, 5-49 cm) at rest and 30 cm (SD, 10; range, 11-69 cm) on Valsalva. Genital hiatus and Pb measured on Valsalva were consistently stronger predictors of prolapse symptoms and objective prolapse (by clinician examination and by ultrasound) than at Gh and Pb measured at rest. The corresponding area under the curve values were significantly larger for Gh/Pb measures on Valsalva after adjusting for multiple confounders.
CONCLUSIONS: Genital hiatus/Pb measured on maximal Valsalva is a superior predictor of symptoms and signs of POP compared with Gh/Pb at rest.
Pelvic organ support several years after a first birth

Ferreira CWS, Atan IK, Martin A, Shek KL, Dietz HP

Int Urogynecol J, 2017 Oct;28(10):1499-1505.
PMID: 28285396 DOI: 10.1007/s00192-017-3297-4

INTRODUCTION AND HYPOTHESIS: Female pelvic organ prolapse is highly prevalent and childbirth has been shown to be an important risk factor. The study was carried out to observe if pelvic organ support deteriorates over time following a first birth.
METHODS: This is a retrospective review using archived data sets of women seen in the context of two prospective perinatal imaging studies. All subjects had undergone a standardised interview, a clinical examination and 4D translabial ultrasound, 3 months and 2-5 years post-partum. Main outcome measures were pelvic organ descent and hiatal area at maximum Valsalva manoeuvre. Means at the two time points were compared using paired Student's t test. Predictors of change over time in continuous variables were explored using linear modelling methods.
RESULTS: A total of 300 women had at least two postnatal follow-ups. They were first seen on average 0.39 (SD 0.2, range 0.2-2.1) years and again 3.1 (SD 1.5, range 1.4-8) years after the index delivery, with a mean interval of 2.71 (SD 1.5, range 0.7-7.7) years, providing a total of 813 (300 × 2.71) woman-years of observation. On univariate analysis, there was a significant decrease in mobility over time of the bladder neck, bladder, and rectal ampulla (P = < 0.004) and hiatal area (P = 0.012). The degree of improvement was less marked in women with levator avulsion.
CONCLUSIONS: A significant reduction in pelvic organ descent and hiatal area was noted over a mean of 2.7 years after a first birth.
Fulltext Bone mineral density in HIV participants randomized to raltegravir and lopinavir/ritonavir compared with standard second line therapy

Martin A, Moore C, Mallon PW, Hoy J, Emery S, Belloso W, et al.

AIDS, 2013 Sep 24;27(15):2403-11.
PMID: 23921615 DOI: 10.1097/01.aids.0000432534.47217.b4

To compare changes over 48 weeks in bone mineral density (BMD) between participants randomized to lopinavir/ritonavir (LPV/r) + raltegravir (RAL) or LPV/r + 2-3 nucleoside/nucleotide reverse transcriptase inhibitors (N(t)RTIs) as second line therapy.
Over-expression of V1A receptors in PVN modulates autonomic cardiovascular control

Lozić M, Tasić T, Martin A, Greenwood M, Šarenac O, Hindmarch C, et al.

Pharmacol Res, 2016 12;114:185-195.
PMID: 27810519 DOI: 10.1016/j.phrs.2016.10.024

The hypothalamic paraventricular nucleus (PVN) is a key integrative site for the neuroendocrine control of the circulation and of the stress response. It is also a major source of the neuropeptide hormone vasopressin (VP), and co-expresses V1a receptors (V1aR). We thus sought to investigate the role of V1aR in PVN in cardiovascular control in response to stress. Experiments were performed in male Wistar rats equipped with radiotelemetric device. The right PVN was transfected with adenoviral vectors (Ads) engineered to over-express V1aR along with an enhanced green fluorescent protein (eGFP) tag. Control groups were PVN transfected with Ads expressing eGFP alone, or wild-type rats (Wt). Rats were recorded with and without selective blockade of V1aR (V1aRX) in PVN under both baseline and stressed conditions. Blood pressure (BP), heart rate (HR), their short-term variabilities, and baroreflex sensitivity (BRS) were evaluated using spectral analysis and the sequence method, respectively. Under baseline physiological conditions,V1aR rats exhibited reduced BRS and a marked increase of BP and HR variability during exposure to stress. These effects were all prevented by V1aRX pretreatment. In Wt rats, V1aRX did not modify cardiovascular parameters under baseline conditions, and prevented BP variability increase by stress. However, V1aRX pretreatment did not modify baroreflex desensitization by stress in either rat strain. It follows that increased expression of V1aR in PVN influences autonomic cardiovascular regulation and demarcates vulnerability to stress. We thus suggest a possible role of hypothalamic V1aR in cardiovascular pathology.
Fulltext Osmoregulation requires brain expression of the renal Na-K-2Cl cotransporter NKCC2

Konopacka A, Qiu J, Yao ST, Greenwood MP, Greenwood M, Lancaster T, et al.

J Neurosci, 2015 Apr 01;35(13):5144-55.
PMID: 25834041 DOI: 10.1523/JNEUROSCI.4121-14.2015

The Na-K-2Cl cotransporter 2 (NKCC2) was thought to be kidney specific. Here we show expression in the brain hypothalamo-neurohypophyseal system (HNS), wherein upregulation follows osmotic stress. The HNS controls osmotic stability through the synthesis and release of the neuropeptide hormone, arginine vasopressin (AVP). AVP travels through the bloodstream to the kidney, where it promotes water conservation. Knockdown of HNS NKCC2 elicited profound effects on fluid balance following ingestion of a high-salt solution-rats produced significantly more urine, concomitant with increases in fluid intake and plasma osmolality. Since NKCC2 is the molecular target of the loop diuretics bumetanide and furosemide, we asked about their effects on HNS function following disturbed water balance. Dehydration-evoked GABA-mediated excitation of AVP neurons was reversed by bumetanide, and furosemide blocked AVP release, both in vivo and in hypothalamic explants. Thus, NKCC2-dependent brain mechanisms that regulate osmotic stability are disrupted by loop diuretics in rats.
Fulltext Author Correction: Perceptions of the appropriate response to norm violation in 57 societies

Eriksson K, Strimling P, Gelfand M, Wu J, Abernathy J, Akotia CS, et al.

Nat Commun, 2021 Apr 26;12(1):2483.
PMID: 33903599 DOI: 10.1038/s41467-021-22955-x
Fulltext Perceptions of the appropriate response to norm violation in 57 societies

Eriksson K, Strimling P, Gelfand M, Wu J, Abernathy J, Akotia CS, et al.

Nat Commun, 2021 03 05;12(1):1481.
PMID: 33674587 DOI: 10.1038/s41467-021-21602-9

Norm enforcement may be important for resolving conflicts and promoting cooperation. However, little is known about how preferred responses to norm violations vary across cultures and across domains. In a preregistered study of 57 countries (using convenience samples of 22,863 students and non-students), we measured perceptions of the appropriateness of various responses to a violation of a cooperative norm and to atypical social behaviors. Our findings highlight both cultural universals and cultural variation. We find a universal negative relation between appropriateness ratings of norm violations and appropriateness ratings of responses in the form of confrontation, social ostracism and gossip. Moreover, we find the country variation in the appropriateness of sanctions to be consistent across different norm violations but not across different sanctions. Specifically, in those countries where use of physical confrontation and social ostracism is rated as less appropriate, gossip is rated as more appropriate.