Interrogating COVID-19 Vaccine Hesitancy in the Philippines with a Nationwide Open-Access Online Survey

To mitigate the unprecedented health, social, and economic damage of COVID-19, the Philippines is undertaking a nationwide vaccination program to mitigate the effects of the global pandemic. In this study, we interrogated COVID-19 vaccine hesitancy in the country by deploying a nationwide open-access online survey, two months before the rollout of the national vaccination program. The Health Belief Model (HBM) posits that people are likely to adopt disease prevention behaviors and to accept medical interventions like vaccines if there is sufficient motivation and cues to action. A majority of our 7,193 respondents (62.5%) indicated that they were willing to be vaccinated against COVID-19. Moreover, multivariable analysis revealed that HBM constructs were associated with vaccination intention in the Philippines. Perceptions of high susceptibility, high severity, and significant benefits were all good predictors for vaccination intent. We also found that external cues to action were important. Large majorities of our respondents would only receive the COVID-19 vaccines after many others had received it (72.8%) or after politicians had received it (68.2%). Finally, our study revealed that most (21%) were willing to pay an amount of PHP1,000 [USD20] for the COVID-19 vaccines with an average willing-to-pay amount of PHP1,892 [USD38].

Ultrasound location of intrauterine devices placed at cesarean section over the first year postpartum.

OBJECTIVES: The primary objective was to measure IUD-fundus and IUD-myometrium distances by ultrasound of IUDs placed during cesarean section over the first year of use. The secondary objective was to determine if these distances are associated with risk of expulsion or removal for side effects. STUDY DESIGN: In this prospective observational study, we performed ultrasounds at six - ten weeks, three months and one year postpartum to measure the distance from the top of the device to the fundal serosa (IUD-fundus) and upper margin of the endometrial cavity (IUD-myometrium). We also assessed IUD expulsion or discontinuation for side effects at each visit. RESULTS: We enrolled 93 women who had copper (n = 77) or levonorgestrel (n = 16) IUDs placed at time of cesarean section. Two patients had complete expulsion, six had partial expulsion and nine requested removal for symptoms. Overall, median IUD-fundus measurements were 2.13 cm (IQR 1.87-2.55) at 6-10 weeks, 1.87 cm (IQR 1.53-2.23) at 3-months and 2.02 cm (IQR 1.67-2.40) at 1-year. Among copper IUD users, distances at six weeks and three months were similar in women who did or did not have expulsion or removal at one year however small numbers limit our ability to assess this relationship. CONCLUSION: We describe the location on ultrasound of IUDs placed at the time of Cesarean section over the first year. We found similar IUD locations at six weeks and three months for participants who did or did not experience expulsion or removal by one year. IMPLICATIONS: Position of intrauterine devices placed during cesarean section was similar for those who did or did not have expulsion or removal for symptoms in the first year after placement. These data may help in the design of future studies to determine if ultrasound measurement of IUDs predicts IUD complications.

An Acute Stress Model in New Zealand White Rabbits Exhibits Altered Immune Response to Infection with West Nile Virus.

The immune competence of an individual is a major determinant of morbidity in West Nile virus (WNV)-infection. Previously, we showed that immunocompetent New Zealand White rabbits (NZWRs; Oryctolagus cuniculus) are phenotypically resistant to WNV-induced disease, thus presenting a suitable model for study of virus-control mechanisms. The current study used corticosteroid-treated NZWRs to model acute "stress"-related immunosuppression. Maximal effects on immune parameters were observed on day 3 post dexamethasone-treatment (pdt). However, contrary to our hypothesis, intradermal WNV challenge at this time pdt produced significantly lower viremia 1 day post-infection (dpi) compared to untreated controls, suggestive of changes to antiviral control mechanisms. To examine this further, RNAseq was performed on RNA extracted from draining lymph node-the first site of virus replication and immune detection. Unaffected by dexamethasone-treatment, an early antiviral response, primarily via interferon (IFN)-I, and induction of a range of known and novel IFN-stimulated genes, was observed. However, treatment was associated with expression of a different repertoire of IFN-α-21-like and IFN-ω-1-like subtypes on 1 dpi, which may have driven the different chemokine response on 3 dpi. Ongoing expression of Toll-like receptor-3 and transmembrane protein-173/STING likely contributed to signaling of the treatment-independent IFN-I response. Two novel genes (putative HERC6 and IFIT1B genes), and the SLC16A5 gene were also highlighted as important component of the transcriptomic response. Therefore, the current study shows that rabbits are capable of restricting WNV replication and dissemination by known and novel robust antiviral mechanisms despite environmental challenges such as stress.

Comparison of Tissue and Blood Concentrations of Oxaliplatin Administrated by Different Modalities of Intraperitoneal Chemotherapy.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new technology for delivering intraperitoneal chemotherapy. It is generally assumed that with PIPAC, the ratio of peritoneal to systemic drug concentration is superior to liquid hyperthermic intraperitoneal chemotherapy (HIPEC). To date, no direct comparative data are available supporting such an assumption. MATERIALS AND METHODS: Twelve 65-day-old pigs were randomly separated into three groups of four pigs each, all of which received intraperitoneal chemotherapy using the following administration methods: PIPAC with oxaliplatin 92 mg in 150 ml dextrose 5% (Group 1); PIPAC with electrostatic aerosol precipitation (ePIPAC; Group 2); or laparoscopic HIPEC (L-HIPEC) with oxaliplatin 400 mg in 4 L dextrose 5% at 42 °C (Group 3). Serial blood and peritoneal tissue concentrations of oxaliplatin were determined by spectrometry. RESULTS: In all three groups, the maximum concentration of oxaliplatin in blood was detected 50-60 min after onset of the chemotherapy experiments, with no significant differences among the three groups (p = 0.7994). Blood oxaliplatin concentrations (0-30 min) were significantly higher in the L-HIPEC group compared with the ePIPAC group (p < 0.05). No difference was found for the overall systemic oxaliplatin absorption (area under the curve). Overall concentrations in the peritoneum were not different among the three groups (p = 0.4725), but were significantly higher in the visceral peritoneum in the PIPAC group (p = 0.0242). CONCLUSIONS: Blood and tissue concentrations were comparable between all groups; however, depending on the intraperitoneal area examined and the time points of drug delivery, the concentrations differed significantly between the three groups.

Cytotoxic effect of different treatment parameters in pressurized intraperitoneal aerosol chemotherapy (PIPAC) on the in vitro proliferation of human colonic cancer cells.

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) has been recently reported as a new approach for intraperitoneal chemotherapy (IPC). By means of a patented micropump, the liquid chemotherapy is delivered into the peritoneal cavity as an aerosol which is supposed to achieve "gas-like" distribution. However, recent data report that the fraction of the submicron aerosol (gas-like) is less than 3 vol% of the total amount of aerosolized chemotherapy. Until today, possible modifications of treatment parameters during PIPAC with the aim of improving therapeutic outcomes have not been studied yet. This study aims to establish an in vitro PIPAC model to explore the cytotoxic effect of the submicron aerosol fraction and to investigate the impact of different application parameters on the cytotoxic effect of PIPAC on human colonic cancer cells. METHODS: An in vitro model using HCT8 colon adenocarcinoma wild-type cells (HCT8WT) and multi-chemotherapy refractory subline (HCT8RT) was established. Different experimental parameters such as pressure, drug dosage, time exposure, and system temperature were monitored in order to search for the conditions with a higher impact on cell toxicity. Cell proliferation was determined by means of colorimetric MTT assay 48 h following PIPAC exposures. RESULTS: Standard operational parameters applied for PIPAC therapy depicted a cytotoxic effect of the submicron aerosol fraction generated by the PIPAC micropump. We also observed that increasing pressure significantly enhanced tumor cell toxicity in both wild-type and chemotherapy-resistant cells. A maximum of cytotoxicity was observed at 15 mmHg. Pressure >15 mmHg did not show additional cytotoxic effect on cells. Increased oxaliplatin dosage resulted in progressively higher cell toxicity as expected. However, in resistant cells, a significant effect was only found at higher drug concentrations. Neither an extension of exposure time nor an increase in temperature of the aerosolized chemotherapy solution added an improvement in cytotoxicity. CONCLUSIONS: In this in vitro PIPAC model, the gas-like PIPAC aerosol fraction showed a cytotoxic effect which was enhanced by higher intra-abdominal pressure with a maximum at 15 mmHg. Similar findings were observed for drug dose escalation. A phase I dose escalation study is currently performed at our institution. However, increasing the intra-abdominal pressure might be a first and simple way to enhance the cytotoxic effect of PIPAC therapy which needs further clinical investigations.

Hyperthermic intracavitary nanoaerosol therapy (HINAT) as an improved approach for pressurised intraperitoneal aerosol chemotherapy (PIPAC): Technical description, experimental validation and first proof of concept.

Background: The delivery of aerosolised chemotherapeutic substances into pressurised capnoperitonea has been reported to be more effective than conventional liquid chemotherapy for the treatment of peritoneal carcinomatosis. However, recent reports reveal limitations of the currently available technology. Material and Methods: A novel approach for pressurised intraperitoneal aerosol chemotherapy (PIPAC), called hyperthermic intracavitary nanoaerosol therapy (HINAT), based on extracavitary generation of hyperthermic and unipolar charged aerosols, was developed. The aerosol size distribution, the spatial drug distribution and in-tissue depth penetration of HINAT were studied by laser diffraction spectrometry, differential electrical mobility analysis, time of flight spectrometry, scintigraphic peritoneography and fluorescence microscopy. All experiments were performed contemporaneous with conventional PIPAC for the purpose of comparison. Furthermore, a first proof of concept was simulated in anesthetised German Landrace pigs. Results: HINAT provides a nanometre-sized (63 nm) unipolar-charged hyperthermic (41 °C) drug aerosol for quasi uniform drug deposition over the whole peritoneum with significantly deeper drug penetration than that offered by conventional PIPAC.

Technical description of the microinjection pump (MIP®) and granulometric characterization of the aerosol applied for pressurized intraperitoneal aerosol chemotherapy (PIPAC).

BACKGROUND: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is gaining acceptance in clinical practice, but detailed information about the microinjection pump (MIP®), the generated aerosol and drug distribution is missing. ANALYTICAL METHODS: Ex vivo granulometric analyses by means of laser diffraction spectrometry were performed for MIP® aerosol characterization. Beside the standard operation conditions, the impact of the volumetric liquid flow rate on the aerosol characteristics was investigated with different liquids. Granulometric results as well as the local drug distribution were verified by ex vivo gravimetric analyses. On the basis of determined MIP® characteristics, the aerosol droplet size, which is necessary for a homogenous intra-abdominal drug distribution, was calculated. RESULTS: Granulometric analyses showed that the MIP® aerosol consists of a bimodal volume-weighted particle size distribution (PSD3) with a median droplet diameter of x 50,3 = 25 µm. Calculations reveal that the droplet size for a homogenous intra-abdominal drug distribution during PIPAC therapy should be below 1.2 µm. We show that >97.5 vol% of the aerosolized liquid is delivered as droplets with ≥3 µm in diameter, which are primarily deposited on the surface beneath the MIP® by gravitational settling and inertial impaction. These findings were confirmed by ex vivo gravimetric analyses, where more than 86.0 vol% of the aerosolized liquid was deposited within a circular area with a diameter of 15 cm. CONCLUSIONS: The granulometric aerosol properties, as well as the aerodynamic conditions achieved by standard MIP® operation, do not support the idea of widespread or homogenous drug distribution in the abdominal cavity.

Evaluating the Effect of Micropump© Position, Internal Pressure and Doxorubicin Dosage on Efficacy of Pressurized Intra-peritoneal Aerosol Chemotherapy (PIPAC) in an Ex Vivo Model.

BACKGROUND/AIM: Pressurized intraperitoneal aerosol chemotherapy (PIPAC) is a novel clinical approach to the treatment of peritoneal carcinomatosis. A well-established, not anatomic ex vivo PIPAC model was used to investigate the influence of changes in internal pressure, distance of the Micropump(©) (MIP) to the distributing surface and the drug concentration on the penetration depth of doxorubicin in the target tissue. MATERIALS AND METHODS: Doxorubicin was aerosolized in an ex vivo PIPAC model using a hermetic container system mimicking the abdominal cavity. Fresh post-mortem swine peritoneum was cut into proportional samples. Tissue specimens were spatially placed at 4 different spots within the box: P1, on the distributing surface of the box, directly opposite to MIP; P2, on the side wall of the box; P3, on the ceiling of the box; P4, on the distributing surface with a partial cover. Impact of changes in the following parameters were analyzed and compared with clinically established values (CEVs) at our center: pressure (CEV=12 mmHg), distance of the MIP from the distributing surface (CEV=8 cm) and doxorubicin concentration (CEV=3 mg/50 ml). In-tissue doxorubicin penetration depth was measured using fluorescence microscopy on frozen thin sections. RESULTS: Tissue positioning in the box had a significant impact on drug penetration after PIPAC with CEV. Under CEV conditions, the highest drug penetration depth was observed in the tissue placed on the distributing surface directly opposite to the MIP (P1: 351 µm, P2: 77 µm, P3: 66 µm, P4: 34 µm). A closer positioning of the MIP lead to a significantly higher mean depth penetration of doxorubicin in the P1 in contrast to other samples in which a reduced drug penetration was observed (1 cm vs. 8 cm distance from MIP to the distributing surface, P1 at 1 cm: 469 µm vs. P1 at 8 cm: 351 µm, p<0.0001; P2 at 1 cm: 25 µm vs. P2 at 8 cm: 77 µm, p<0.0001; P3 at 1 cm: 21 µm vs. P3 at 8 cm: 66 µm, p<0.001; P4 at 1 cm: 13 µm vs. P4 at 8 cm: 39 µm, p=0.021). Higher doxorubicin concentrations led to a highly significant increase of drug penetration in P1 (1 cm vs. 8 cm, p<0.0001), but only a little significant increase in other samples. An increase of internal pressure did not show a significant increase in penetration depth of doxorubicin. CONCLUSION: Our ex vivo data suggest that a higher pressure does not increase the penetration deepness of doxorubicin. Higher drug dosage and a closer positioning of the MIP toward the target lead to a higher penetration of doxorubicin within the samples. A more homogeneous penetration within all targets cannot be achieved by changing drug concentration, position of the nozzle or pressure increase.

Hyperandrogenism Accompanies Increased Intra-Abdominal Fat Storage in Normal Weight Polycystic Ovary Syndrome Women.

CONTEXT: Normal weight polycystic ovary syndrome (PCOS) women may have altered adipose structure-function underlying metabolic dysfunction. OBJECTIVE: This study examines whether adipose structure-functional changes exist in normal weight PCOS women and correlate with hyperandrogenism and/or hyperinsulinemia. DESIGN: This is a prospective cohort study. SETTING: The setting was an academic medical center. PATIENTS: Six normal weight PCOS women and 14 age- and body mass index-matched normoandrogenic ovulatory (NL) women were included. INTERVENTION(S): All women underwent circulating hormone and metabolic measurements; frequently sampled intravenous glucose tolerance testing; total body dual-energy x-ray absorptiometry; abdominal magnetic resonance imaging; and SC abdominal fat biopsy. MAIN OUTCOME MEASURE(S): Circulating hormones and metabolites, body fat and its distribution, and adipocyte size were compared between PCOS and NL women, and were correlated with each other in all women. RESULTS: Circulating LH and androgen levels were significantly greater in PCOS than NL women, as were fasting insulin levels, pancreatic ß-cell responsiveness to glucose, and total abdominal fat mass. Intra-abdominal fat mass also was significantly increased in PCOS women and was positively correlated with circulating androgen, fasting insulin, triglyceride, and non-high-density lipoprotein cholesterol levels in all women. SC abdominal fat mass was not significantly increased in PCOS women, but contained a greater proportion of small SC abdominal adipocytes that positively correlated with serum androgen levels in all women. CONCLUSION: Hyperandrogenism in normal weight PCOS women is associated with preferential intra-abdominal fat deposition and an increased population of small SC abdominal adipocytes that could constrain SC adipose storage and promote metabolic dysfunction.

Prothymosin α variants isolated from CD8+ T cells and cervicovaginal fluid suppress HIV-1 replication through type I interferon induction.

Soluble factors from CD8(+) T cells and cervicovaginal mucosa of women are recognized as important in controlling human immunodeficiency virus type 1 (HIV-1) infection and transmission. Previously, we have shown the strong anti-HIV-1 activity of prothymosin α (ProTα) derived from CD8(+) T cells. ProTα is a small acidic protein with wide cell distribution, to which several functions have been ascribed, depending on its intracellular or extracellular localization. To date, activities of ProTα have been attributed to a single protein known as isoform 2. Here we report the isolation and identification of 2 new ProTα variants from CD8(+) T cells and cervicovaginal lavage with potent anti-HIV-1 activity. The first is a splice variant of the ProTα gene, known as isoform CRA_b, and the second is the product of a ProTα gene, thus far classified as a pseudogene 7. Native or recombinant ProTα variants potently restrict HIV-1 replication in macrophages through the induction of type I interferon. The baseline expression of interferon-responsive genes in primary human cervical tissues positively correlate with high levels of intracellular ProTα, and the knockdown of ProTα variants by small interfering RNA leads to downregulation of interferon target genes. Overall, these findings suggest that ProTα variants are innate immune mediators involved in immune surveillance.

Accelerating dynamic magnetic resonance imaging (MRI) for lung tumor tracking based on low-rank decomposition in the spatial-temporal domain: a feasibility study based on simulation and preliminary prospective undersampled MRI.

PURPOSE: To evaluate a low-rank decomposition method to reconstruct down-sampled k-space data for the purpose of tumor tracking. METHODS AND MATERIALS: Seven retrospective lung cancer patients were included in the simulation study. The fully-sampled k-space data were first generated from existing 2-dimensional dynamic MR images and then down-sampled by 5 × -20 × before reconstruction using a Cartesian undersampling mask. Two methods, a low-rank decomposition method using combined dynamic MR images (k-t SLR based on sparsity and low-rank penalties) and a total variation (TV) method using individual dynamic MR frames, were used to reconstruct images. The tumor trajectories were derived on the basis of autosegmentation of the resultant images. To further test its feasibility, k-t SLR was used to reconstruct prospective data of a healthy subject. An undersampled balanced steady-state free precession sequence with the same undersampling mask was used to acquire the imaging data. RESULTS: In the simulation study, higher imaging fidelity and low noise levels were achieved with the k-t SLR compared with TV. At 10 × undersampling, the k-t SLR method resulted in an average normalized mean square error <0.05, as opposed to 0.23 by using the TV reconstruction on individual frames. Less than 6% showed tracking errors >1 mm with 10 × down-sampling using k-t SLR, as opposed to 17% using TV. In the prospective study, k-t SLR substantially reduced reconstruction artifacts and retained anatomic details. CONCLUSIONS: Magnetic resonance reconstruction using k-t SLR on highly undersampled dynamic MR imaging data results in high image quality useful for tumor tracking. The k-t SLR was superior to TV by better exploiting the intrinsic anatomic coherence of the same patient. The feasibility of k-t SLR was demonstrated by prospective imaging acquisition and reconstruction.

Radical prostatectomy: value of prostate MRI in surgical planning.

The introduction of serum prostate-specific antigen to the prostate cancer screening algorithm has led to an increase in prostate cancer diagnosis as well as a migration toward lower-stage cancer at the time of diagnosis. This stage migration has coincided with changes in treatment options; these include active surveillance, new therapies, and advances in surgical techniques. Use of robot-assisted radical prostatectomy (RARP) as a surgical technique has seen a significant increase over the past several years: the number of patients undergoing RARP has risen from 1% to 40% of all prostatectomies from 2001-2006 to as many as 80% in 2010. The robotic interface provides a 3D magnified view of the surgical field, intuitive instrument manipulation, motion scaling, tremor filtration, and excellent dexterity and range of motion. However, in some cases, the lack of tactile (haptic) feedback may limit the surgeon's decision making ability in assessing malignant involvement of the neurovascular bundles. Pre-operative planning relies on nomograms based on limited clinical and prostate biopsy information. The surgical decision to spare or resect the neurovascular bundles is based on clinical information which is not spatially or anatomically based. Advances in magnetic resonance imaging (MRI) may provide spatially localized information to fill this void and aid surgical planning, particularly for robotic surgeons. In this review, we discuss the potential role of pre-operative MRI in surgical planning for radical prostatectomy.

Continuing the definition of death debate: the report of the president's council on bioethics on controversies in the determination of death.

The President's Council on Bioethics has recently released a report supportive of the continued use of brain death as a criterion for human death. The Council's conclusions were based on a conception of life that stressed external work as the fundamental marker of organismic life. With respect to human life, it is spontaneous respiration in particular that indicates an ability to interact with the external environment, and so indicates the presence of life. Conversely, irreversible apnoea marks an inability to carry out the necessary work of life, an inability which the Council considers an indicator of death. This conception has been conceived to circumvent criticisms of the previous model of loss of somatic integration, a model the Council admits that, in the presence of evidence of continuing functional integration in brain dead patients, was looking less than convincing. Nevertheless, by focusing on external work and ignoring the more essential work of integrative unity, the Council's conception of the nature of life is untenable, and of no assistance in supporting a relation of equivalence between the concepts of brain death and death. Consequently, the Council's conclusions do little to advance the definition of death debate, a potentially intractable debate that may necessitate the investigation of alternate ethical justifications for organ harvesting.

Diversity of endophytic yeasts from sweet orange and their localization by scanning electron microscopy.

Endophytes are microorganisms that colonize plant tissues internally without causing harm to the host. Despite the increasing number of studies on sweet orange pathogens and endophytes, yeast has not been described as a sweet orange endophyte. In the present study, endophytic yeasts were isolated from sweet orange plants and identified by sequencing of internal transcribed spacer (ITS) rRNA. Plants sampled from four different sites in the state of São Paulo, Brazil exhibited different levels of CVC (citrus variegated chlorosis) development. Three citrus endophytic yeasts (CEYs), chosen as representative examples of the isolates observed, were identified as Rhodotorula mucilaginosa, Pichia guilliermondii and Cryptococcus flavescens. These strains were inoculated into axenic Citrus sinensis seedlings. After 45 days, endophytes were re-isolated in populations ranging from 10(6) to 10(9) CFU/g of plant tissue, but, in spite of the high concentrations of yeast cells, no disease symptoms were observed. Colonized plant material was examined by scanning electron microscopy (SEM), and yeast cells were found mainly in the stomata and xylem of plants, reinforcing their endophytic nature. P. guilliermondii was isolated primarily from plants colonized by the causal agent of CVC, Xylella fastidiosa. The supernatant from a culture of P. guilliermondii increased the in vitro growth of X. fastidiosa, suggesting that the yeast could assist in the establishment of this pathogen in its host plant and, therefore, contribute to the development of disease symptoms.

Transmission of Methylobacterium mesophilicum by Bucephalogonia xanthophis for paratransgenic control strategy of citrus variegated chlorosis.

Methylobacterium mesophilicum, originally isolated as an endophytic bacterium from citrus plants, was genetically transformed to express green fluorescent protein (GFP). The GFP-labeled strain of M. mesophilicum was inoculated into Catharanthus roseus (model plant) seedlings and further observed colonizing its xylem vessels. The transmission of this endophyte by Bucephalogonia xanthophis, one of the insect vectors that transmit Xylella fastidiosa subsp. pauca, was verified by insects feeding from fluids containing the GFP bacterium followed by transmission to plants and isolating the endophyte from C. roseus plants. Forty-five days after inoculation, the plants exhibited endophytic colonization by M. mesophilicum, confirming this bacterium as a nonpathogenic, xylem-associated endophyte. Our data demonstrate that M. mesophilicum not only occupy the same niche of X. fastidiosa subsp. pauca inside plants but also may be transmitted by B. xanthophis. The transmission, colonization, and genetic manipulation of M. mesophilicum is a prerequisite to examining the potential use of symbiotic control to interrupt the transmission of X. fastidiosa subsp. pauca, the bacterial pathogen causing Citrus variegated chlorosis by insect vectors.

Focal subcortical biophysical abnormalities in patients diagnosed with type 2 diabetes and depression.

CONTEXT: Major depressive disorder has been consistently identified in patients with type 2 diabetes. Despite its high prevalence and clinical effect, the neurobiological substrates underlying depression in patients with diabetes remain largely unknown. OBJECTIVE: To examine the biophysical integrity of proteins in critical white and gray matter regions in patients with type 2 diabetes and major depression to understand the pathophysiology of depression in diabetes. DESIGN: A cross-sectional magnetization transfer study using magnetic resonance imaging. Regions examined included the anterior cingulate, corpus callosum, frontal and occipital white matter, and the caudate and lenticular nuclei. SETTING: A tertiary care university hospital. PARTICIPANTS: We studied 16 patients diagnosed with type 2 diabetes and major depression, 22 patients diagnosed with diabetes without depression (diabetic controls), and 30 controls without diabetes or major depression (healthy controls). MAIN OUTCOME MEASURES: Magnetization transfer ratios, a measure of the biophysical structure of proteins in the gray and white matter. RESULTS: Magnetization transfer ratios were significantly lower bilaterally in the head of the caudate nucleus in the group with diabetes and depression compared with the other 2 groups (P < .001). Diabetic controls had values between the depressed diabetic and healthy control groups. There were no significant differences in magnetization transfer ratios between groups in the other regions examined. CONCLUSIONS: These data indicate that there is an important subcortical biophysical component to depression in patients with type 2 diabetes. This finding has broad implications for the neuronal circuitry underlying mood disorders.

Prefrontal myo-inositol concentration and visuospatial functioning among diabetic depressed patients.

Patients with diabetes mellitus are reported to be at higher risk for developing neuropsychiatric disorders such as dementia and depression. Myo-inositol (mI), a neuronal/glial metabolite associated with multiple functions in the brain, has been shown to be increased in cognitive disorders, depression and diabetes. This study examined whether elevations in dorsolateral (DL) mI of diabetic patients with depression were associated with visuospatial deficits. Diabetic and depressed patients (n=18) were matched with patients with diabetes but without depression (n=20) and control subjects (n=19). Subjects were scored on both the recall and recognition tasks of the Rey-Osterreith Complex Figure (ROCF). Proton magnetic spectroscopy spectra from bilateral prefrontal white matter voxels were used to obtain concentrations of mI. Controls showed negative correlations between mI in right DL white matter and recall and recognition subtests. No correlation was observed for depressed diabetic patients. Correlations for diabetic controls fell midway between the comparison and depressed diabetic groups. The expected pattern of association between mI and visuospatial impairment in the right DL prefrontal region was seen among healthy controls. Progressive weakening of this association across both diabetic groups might be related to progressive changes in neural activity that underlies visuospatial function.

Concentration of depot medroxyprogesterone acetate and pain scores in adolescents: a randomized clinical trial.

A prospective, single-blinded, randomized trial was initiated to determine whether injection site pain differed in adolescents receiving two concentrations of 150 mg of depot medroxyprogesterone acetate (DMPA). Ninety-five adolescents seeking injectable contraception were randomized to receive 150 mg of DMPA as follows: a deltoid injection of 1.0 mL from a single-unit-dose vial containing 150 mg/mL or 0.38 mL from a multidose vial containing 400 mg/mL of DMPA. A visual analogue scale was measured at each visit and cumulatively compared between the groups. Continuation rates were tabulated. The report of pain for the multidose vial group was significantly higher than for the unit-dose vial group (p<.003). The dropout rates for both groups were high at 1 year and were not statistically different (multidose group=64% and unit-dose group=77%). Twenty percent of the subjects in the multidose group vs. 22% in the unit-dose group discontinued due to bleeding irregularities. The concentrated form of DMPA led to greater pain at the injection site than did the less concentrated form, but this did not lead to higher discontinuation rates among adolescents.

Frequency of douching and risk of bacterial vaginosis in African-American women.

OBJECTIVE: Frequent vaginal douching has been associated with bacterial vaginosis. We investigated whether infrequent douching is also a risk factor for bacterial vaginosis. METHODS: In this cross-sectional study, we recruited 411 African-American women of reproductive age who were visiting gynecologic or family planning clinics of 2 hospitals in New York City from 1999 to 2001. Detailed information on demographic characteristics, feminine hygiene practice, contraceptive use, and reproductive and medical history was collected through in-person interview. Pelvic examinations and laboratory tests on vaginal secretions were performed. Bacterial vaginosis was defined as Gram stain score of 7 or greater. RESULTS: The overall prevalence of bacterial vaginosis in this population was 27%, similar to the national average. Water-vinegar solution was the most common douche. Although one half of the subjects reported douching regularly, only 2% douched frequently (once per week or more). Frequent douching in the past 3 months had a prevalence ratio of bacterial vaginosis of 2.35 (95% confidence interval 0.98-5.63). However, douching less than once per week was not associated with bacterial vaginosis. CONCLUSION: Douching less than once per week, particularly with a water-vinegar douche, is not associated with bacterial vaginosis in this African-American population. LEVEL OF EVIDENCE: III