Contraceptive use and method mix dynamics in Sub-saharan Africa: time trends and the influence of the HIV pandemic.

BACKGROUND: Contraceptive use dynamics continue to be of priority in sub-Saharan Africa because of persistently high levels of fertility. This paper focuses on the use of barrier versus non-barrier contraceptive use in sub-Saharan Africa hypothesizing that the HIV pandemic in the region would be responsible for increases in the use of barrier methods over time. METHODS: This paper uses Demographic and Heath Survey (DHS) data from 32 countries to conduct extensive analysis of trends in contraceptive use and method mix that refers to the distribution of contraceptive methods use among the sexually active population. The paper examines how contraceptive method mix dynamics have changed over time and whether the trends differ by marital status and gender using cross-tabulations. It furthers examines the determinants of method choice using logistic regressions. RESULTS: The findings indicate that the use of barrier methods, most markedly for unmarried women and men, rose substantially between the late 1980s and late 2000s in the region in tandem with trends in HIV prevalence. The results further show marked differences in method mix by gender with men being more likely to report barrier method use than women. CONCLUSIONS: The findings indicate shifting preferences in contraceptive choice. The time trend analyses highlight the importance of expanding the focus of contraceptive use studies beyond women in this context as the study finds differing trends for men.

Bilateral, Simultaneous Central Serous Chorioretinopathy in Association With Oral Contraception Use.

This report describes a case of bilateral, simultaneous central serous chorioretinopathy (CSCR) in a young woman on oral contraceptive pills (OCP). A 21-year-old woman with a negative past medical history presented with sudden onset of bilateral decreased vision shortly after starting OCP. Comprehensive ocular examination revealed bilateral central serous chorioretinopathy (CSCR), confirmed on retinal optical coherence tomography (OCT) and intravenous fluorescein angiography. The patient was instructed to discontinue OCP, and three weeks later, there was complete resolution of the visual symptoms and of the bilateral serous retinal detachments, documented on OCT. [Ophthalmic Surg Lasers Imaging Retina 2024;55:96-99.].

A Rare Case of Vomiting-Induced Retrobulbar Hemorrhage.

Retrobulbar hemorrhage may result in sudden accumulation of blood in the retrobulbar space which can lead to an orbital compartment syndrome. This potentially blinding condition is characterized by a rapid increase in intra-orbital pressure. While most commonly associated with orbital trauma, it may rarely occur with Valsalva events in patients on anticoagulants. In this report, we present a case of a retrobulbar hemorrhage secondary to self-induced vomiting, occurring in a patient on no anticoagulation medication.

The nervous system: Orchestra conductor in cancer, regeneration, inflammation and immunity.

Although the role of nerves in stimulating cellular growth and dissemination has long been described in tissue regeneration studies, until recently a similar trophic role of nerves in disease was not well recognized. However, recent studies in oncology have demonstrated that the growth and dissemination of cancers also requires the infiltration of nerves in the tumor microenvironment. Nerves generate various neurosignaling pathways, which orchestrate cancer initiation, progression, and metastases. Similarly, nerves are increasingly implicated for their regulatory functions in immunity and inflammation. This orchestrator role of nerves in cellular and molecular interactions during regeneration, cancer, immunity, and inflammation offers new possibilities for targeting or enhancing neurosignaling in human health and diseases.

Phase 1 Study of Low-Dose Fractionated Whole Abdominal Radiation Therapy in Combination With Weekly Paclitaxel for Platinum-Resistant Ovarian Cancer (GCGS-01).

PURPOSE: Low-dose fractionated whole abdominal radiation therapy (LDFWART) has synergistic activity with paclitaxel in preclinical models. The aim of this phase 1 trial was to determine the recommended phase 2 dose and preliminary activity of weekly paclitaxel (wP) concurrent with LDFWART in patients with platinum-resistant ovarian cancer (PROC). METHODS AND MATERIALS: Patients were enrolled at de-escalating dose levels of wP (part A), starting at 80 mg/m2, concurrent with fixed-dose LDFWART delivered in 60 cGy fractions twice-daily, 2 days per week, for 6 continuous weeks. After completing the 6-week course of wP + LDFWART, patients received wP until disease progression. Dose-limiting toxicity was evaluated during the first 3 weeks of wP + LDFWART. At wP (80 mg/m2) + LDFWART, no dose-limiting toxicities were observed; this was the established maximum tolerated dose. The trial was expanded (part B) with 7 additional patients with platinum-resistant, high-grade serous ovarian cancer to confirm toxicity and activity. RESULTS: A total of 10 heavily pretreated patients were recruited (3 patients to part A, 7 patients to part B). They had received a median of 5 prior lines of therapy, and 70% of patients had received prior wP; 60% of patients completed 6 weeks of wP + LDFWART. Common related grade ≥3 adverse events were neutropenia (60%) and anemia (30%). Median progression-free survival was 3.2 months, and overall survival was 13.5 months. Of patients evaluable for response, 33% (3 of 9) achieved confirmed biochemical response (CA125 decrease >50% from baseline), 11% (1) achieved a partial response, and 5 patients had stable disease, giving a disease control rate of 66.7% (6 of 9). Four patients had durable disease control of ≥12 weeks, completing 12 to 21 weeks of wP. CONCLUSIONS: The recommended phase 2 dose of wP + LDFWART for 6 weeks is 80 mg/m2. Encouraging efficacy in heavily pretreated PROC patients was observed, suggesting that further development of this therapeutic strategy in PROC should be considered.

The A-Effect and Global Motion.

When the head is tilted, an objectively vertical line viewed in isolation is typically perceived as tilted. We explored whether this shift also occurs when viewing global motion displays perceived as either object-motion or self-motion. Observers stood and lay left side down while viewing (1) a static line, (2) a random-dot display of 2-D (planar) motion or (3) a random-dot display of 3-D (volumetric) global motion. On each trial, the line orientation or motion direction were tilted from the gravitational vertical and observers indicated whether the tilt was clockwise or counter-clockwise from the perceived vertical. Psychometric functions were fit to the data and shifts in the point of subjective verticality (PSV) were measured. When the whole body was tilted, the perceived tilt of both a static line and the direction of optic flow were biased in the direction of the body tilt, demonstrating the so-called A-effect. However, we found significantly larger shifts for the static line than volumetric global motion as well as larger shifts for volumetric displays than planar displays. The A-effect was larger when the motion was experienced as self-motion compared to when it was experienced as object-motion. Discrimination thresholds were also more precise in the self-motion compared to object-motion conditions. Different magnitude A-effects for the line and motion conditions-and for object and self-motion-may be due to differences in combining of idiotropic (body) and vestibular signals, particularly so in the case of vection which occurs despite visual-vestibular conflict.

A comparative study between the pioneer cohort of waterbirths and conventional vaginal deliveries in an obstetrician-led unit in Singapore.

OBJECTIVE: Waterbirth has been increasing in popularity in Asia (Lea W. Water babies. The Straits Times 17 February 2011. Available at http://www.nuh.com.sg/news/media-articles_1504.html). National University Hospital, Singapore, is the pioneer hospital offering waterbirths to women since 2006 in a unique setting of a consultant-led service and continuous foetal monitoring. To date, no studies have been done on the conduct of waterbirths in an Asia. This study aims to evaluate if water immersion during delivery is associated with increased rates of adverse maternal and foetal outcomes as compared with conventional vaginal deliveries. MATERIALS AND METHODS: Clinical records of women who birthed underwater at National University Hospital between 2010 and 2013 were retrospectively reviewed. Outcomes of interest were estimated blood loss, third- or fourth degree tears, incidence of postpartum infections or haemorrhage, neonatal Apgars at 1 and 5 min, and neonatal complications requiring intensive care unit admission. Outcomes were compared against a matched control group of women who had conventional vaginal deliveries within ≤1 month. RESULTS: Records of 118 women who birthed underwater were accrued. There was no significant difference in estimated blood loss and postpartum haemorrhage between groups, and there were no cases of maternal infection, third- or fourth-degree perineal tears, or adverse neonatal outcomes in either group. Women in the control group were more likely to have episiotomies (63.6% vs. 0.85%; p < 0.01). Three cases of retained placenta were reported in the waterbirth group (0.03%). CONCLUSION: Waterbirth at our centre does not appear to be associated with an increased incidence of adverse neonatal and maternal outcomes. The results of this study supported waterbirth as a birthing option to groups of low-risk women in an obstetrician-led setting with good midwifery support.

The Effect of Health Literacy on Medication Knowledge and Medication Discrepancy in Chinese Americans.

Background. Functional health literacy (FHL) is increasingly recognized as a useful predictor of health outcomes in different populations. However, the effect of FHL on medication knowledge and medication discrepancy in Chinese Americans is not well defined. Objectives. To examine the effects of FHL on medication knowledge and medication discrepancy in Chinese American patients. Methods. This was a cross-sectional study conducted at an academic internal medicine clinic. The Short Test of Functional Health Literacy in Adults was used to assess participants' FHL. Data for patients' demographic information, medication knowledge, and medication discrepancy (direction discrepancy and name discrepancy) were collected through patient interviews and chart reviews. The primary outcome was medication knowledge of purpose and the secondary outcomes included medication direction discrepancy and medication name discrepancy. Results. Of the 158 Chinese American patients who participated in the study, 54% had adequate FHL. More participants with adequate FHL had correct medication knowledge compared to participants with inadequate FHL (87% vs 56%, respectively, odds ratio = 3.4, 95% confidence interval = 1.2-9.7). Fewer participants with adequate FHL had medication direction discrepancy compared to those with inadequate FHL (42% vs 62%, odds ratio = 0.18, 95% confidence interval = 0.06-0.55). Both adequate and inadequate FHL groups had high prevalence of medication name discrepancy (77% vs 89%) even though the between-group difference was insignificant. Conclusions. Adequate FHL among Chinese American patients is significantly associated with increased medication knowledge of purpose and decreased medication direction discrepancy. Both adequate and inadequate FHL groups had high prevalence of medication name discrepancy.

SMN deficiency alters Nrxn2 expression and splicing in zebrafish and mouse models of spinal muscular atrophy.

Spinal muscular atrophy (SMA) is a progressive neurodegenerative disease affecting lower motor neurons. SMA is caused by mutations in the Survival Motor Neuron 1 (SMN1) gene, which result in reduced levels of functional SMN protein. Biochemical studies have linked the ubiquitously expressed SMN protein to the assembly of pre-mRNA processing U snRNPs, raising the possibility that aberrant splicing is a major defect in SMA. Accordingly, several transcripts affected upon SMN deficiency have been reported. A second function for SMN in axonal mRNA transport has also been proposed that may likewise contribute to the SMA phenotype. The underlying etiology of SMA, however, is still not fully understood. Here, we have used a combination of genomics and live Ca(2+) imaging to investigate the consequences of SMN deficiency in a zebrafish model of SMA. In a transcriptome analyses of SMN-deficient zebrafish, we identified neurexin2a (nrxn2a) as strongly down-regulated and displaying changes in alternative splicing patterns. Importantly, the knock-down of two distinct nrxn2a isoforms phenocopies SMN-deficient fish and results in a significant reduction of motor axon excitability. Interestingly, we observed altered expression and splicing of Nrxn2 also in motor neurons from the Smn(-/-);SMN2(+/+) mouse model of SMA, suggesting conservation of nrxn2 regulation by SMN in mammals. We propose that SMN deficiency affects splicing and abundance of nrxn2a. This may explain the pre-synaptic defects at neuromuscular endplates in SMA pathophysiology.

Perception of smooth and perturbed vection in short-duration microgravity.

Successful adaptation to the microgravity environment of space and readaptation to gravity on earth requires recalibration of visual and vestibular signals. Recently, we have shown that adding simulated viewpoint oscillation to visual self-motion displays produces more compelling vection (despite the expected increase in visual-vestibular conflict experienced by stationary observers). Currently, it is unclear what role adaptation to gravity might play in this oscillation-based vection advantage. The vection elicited by optic flow displays simulating either smooth forward motion or forward motion perturbed by viewpoint oscillation was assessed before, during and after microgravity exposure in parabolic flight. During normal 1-g conditions subjects experienced significantly stronger vection for oscillating compared to smooth radial optic flow. The magnitude of this oscillation enhancement was reduced during short-term microgravity exposure, more so for simulated interaural (as opposed to spinal) axis viewpoint oscillation. We also noted a small overall reduction in vection sensitivity post-flight. A supplementary experiment found that 1-g vection responses did not vary significantly across multiple testing sessions. These findings: (i) demonstrate that the oscillation advantage for vection is very stable and repeatable during 1-g conditions and (ii) imply that adaptation or conditioned responses played a role in the post-flight vection reductions. The effects observed in microgravity are discussed in terms of the ecology of terrestrial locomotion and the nature of movement in microgravity.

Influence of head orientation and viewpoint oscillation on linear vection.

Sensory conflict theories predict that adding simulated viewpoint oscillation to self-motion displays should generate significant and sustained visual-vestibular conflict and reduce the likelihood of illusory self-motion (vection). However, research shows that viewpoint oscillation enhances vection in upright observers. This study examined whether the oscillation advantage for vection depends on head orientation with respect to gravity. Displays that simulated forward/backward self-motion with/without horizontal and vertical viewpoint oscillation were presented to observers in upright (seated and standing) and lying (supine, prone, and left side down) body postures. Viewpoint oscillation was found to enhance vection for all of the body postures tested. Vection also tended to be stronger in upright postures than in lying postures. Changing the orientation of the head with respect to gravity was expected to alter the degree/saliency of the sensory conflict, which may explain the overall posture-based differences in vection strength. However, this does not explain why the oscillation advantage for vection persisted for all postures. Thus, the current postural and oscillation based vection findings appear to be better explained by ecology: Upright postures and oscillating flow (that are the norm during self-motion) improved vection, whereas lying postures and smooth optic flows (which are less common) impaired vection.

Double down for a double win.

The rationale for using multiple inhibitors between and within the phosphoinositide 3-kinase/AKT/mTOR and RAS/MEK/ERK pathways is scientifically compelling, and a limited number of experimental agents are currently being tested in phase I combinations. Patient subpopulations, whose tumors are defined by genetic lesions, are showing promising responses to this approach.

Poststreptococcal keratouveitis associated with group C streptococcus pharyngitis.

PURPOSE: To report the first case of poststreptococcal syndrome uveitis (PSU) in association with group C streptococcus (GCS). PATIENTS AND METHODS: Chart review of a 24-year-old man who presented with bilateral ocular redness, pain, and photophobia for 5 days and "white rings" around his eyes for a duration of 3 days. The patient further reported fever and sore throat in the preceding week. Slit-lamp examination showed bilateral keratouveitis. A thorough uveitis workup, antistreptolysin O (ASLO) titer, and throat culture were obtained. The patient was treated with frequent topical steroids and systemic doxycycline. The uveitis and keratitis subsided over the next few weeks, leaving extensive peripheral keratolysis. RESULTS: The results of laboratory diagnostic testing revealed an elevated ASLO, C-reactive protein, as well as HLA-B27 positivity. Throat cultures grew beta-hemolytic GCS; group A streptococcus was culture negative. CONCLUSION: GCS pharyngitis may be a causative organism of PSU.

A novel calpain inhibitor for treatment of transient retinal ischemia in the rat.

After an acute ischemia/reperfusion of the rat retina, the activation of cytotoxic proteases, including calpain, results in necrosis and apoptosis of retinal ganglion cells resulting in their degeneration. Using a systemically administered calpain inhibitor that crosses the blood-retinal barrier would provide for novel systemic intervention that protects the retina from acute injury and loss of function. Herein, we study a novel calpain peptide inhibitor, cysteic-leucyl-argininal (CYLA), in an in-vivo rat model of retinal ischemia to determine functional protection using electroretinography. The CYLA prodrug was administered intraperitoneally before and/or after ischemia-reperfusion at concentrations of 20-40 mg/kg. We found that administering 20 mg/kg of CYLA only after ischemia provides significant preservation of retinal function.

A proposal: a comprehensive platform to characterize tumors in Chinese and improve success in cancer drug discovery and development.

Cancer is a collection of complex diseases in which cell proliferation and apoptosis are dysregulated due to the acquisition of genetic changes in cancer cells. These genetic changes, combined with the interrelated physiologic adaptations of neo-angiogenesis, recruitment of stromal support tissues, and suppression of immune recognition, are measurable characteristics in tumor gene expression profiles and biochemical pathways. These measures can lead to identification of disease drivers and, ultimately, can be used to assign therapy. With advances in RNA sequencing technologies, the ability to simultaneously measure all genetic and gene expression changes with a single technology is now possible. The ability to create a comprehensive catalog of genotypic and phenotypic changes in a collection of histologically similar but otherwise distinct tumors should allow for a more precise positioning of existing targeted therapies and identification of new targets for intervention.

EMT is the dominant program in human colon cancer.

BACKGROUND: Colon cancer has been classically described by clinicopathologic features that permit the prediction of outcome only after surgical resection and staging. METHODS: We performed an unsupervised analysis of microarray data from 326 colon cancers to identify the first principal component (PC1) of the most variable set of genes. PC1 deciphered two primary, intrinsic molecular subtypes of colon cancer that predicted disease progression and recurrence. RESULTS: Here we report that the most dominant pattern of intrinsic gene expression in colon cancer (PC1) was tightly correlated (Pearson R = 0.92, P < 10(-135)) with the EMT signature-- both in gene identity and directionality. In a global micro-RNA screen, we further identified the most anti-correlated microRNA with PC1 as MiR200, known to regulate EMT. CONCLUSIONS: These data demonstrate that the biology underpinning the native, molecular classification of human colon cancer--previously thought to be highly heterogeneous-- was clarified through the lens of comprehensive transcriptome analysis.