Although extensive research has found a strong relationship between poor family functioning and d... more Although extensive research has found a strong relationship between poor family functioning and depression, previous research has not examined this relationship among low-income Latinos. In this study, we examined how family functioning may be associated with depression in a sample of low-income Latino couples. In addition, we examined how acculturative stress moderates the relationship between family functioning and depression. Our results indicate that the relationship between family functioning and depression is stronger in women and that acculturative stress moderates this relationship in women. Probing this interaction indicates that women who reported high acculturative stress coupled with poor family functioning experienced more depression. Clinical implications are discussed.
This paper describes the experiences of the first author and his colleagues in the development an... more This paper describes the experiences of the first author and his colleagues in the development and implementation of a depression prevention program that specifically targets Latina mothers. Building on the earlier papers that highlight the underutilization of mental health services by Latinos in general, this paper will make the case that the situation is particularly concerning with regards to depression. In addition to the fact that depression is a highly prevalent disorder among Latino adults, the potential consequences for children of parents with depression are significant. Thus, the underutilization of formal mental health services by Latinos makes depression a critical public health problem that calls for creative solutions. One possible solution is the careful development and implementation of prevention programs. Depression prevention programs have some advantages over formal mental health treatment in that they can be offered at a relatively low cost, can be packaged in ways that make them less stigmatizing, and if effective, can reduce the incidence of cases that develop into clinical depression.This paper will describe the process of developing a novel depression prevention program, with a particular focus on the attention paid to cultural sensitivity. We describe the complexity inherent in defining cultural sensitivity and illustrate in concrete ways its implementation in the development and evaluation of the prevention program. In addition, we explore some of the challenges that emerge when attempting to balance the creation of a program that is culturally sensitive with the demands of rigorous quantitative evaluation.
Estrogen therapy (ET) seems to differentially effect cognitive processes in younger versus older ... more Estrogen therapy (ET) seems to differentially effect cognitive processes in younger versus older postmenopausal women, suggesting a window of opportunity when ET is most beneficial. Cognitive improvement in younger postmenopausal women has been attributed to ET's influence on hot flushes and sleep, but empiric examination of the mediating role of menopause symptoms versus direct effects of ET on the brain is limited. In a double-blind trial, 52 women were randomly assigned to estradiol 0.05 mg/day (n = 26) or placebo transdermal patches (n = 26) for 12 weeks. Women completed tests of memory, learning, and executive functioning, and hot flush and sleep assessments at baseline and study end. A subset of women (five ET treated, six placebo treated) also underwent blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies. Nondepressed perimenopausal and postmenopausal women were studied. The majority had hot flushes and sleep impairment. Compared with placebo, ET selectively reduced errors of perseveration during verbal recall (P = 0.03), a frontal system-mediated function, but did not influence other cognitive processes. Women with baseline hot flushes had greater cognitive benefit with ET (P < 0.05). Cognitive benefit was not associated with sleep problems or its improvement. Measures of fMRI BOLD activation during tests of verbal and spatial working memory showed significant increases in frontal system activity with ET (P < 0.001). Estrogen therapy selectively improves executive functioning as demonstrated by reduced perseverative errors and prefrontal cortex activation during verbal recall tasks. Cognitive improvement with ET is associated with hot flushes, but not with sleep, suggesting that ET has a direct central nervous system effect, rather than an indirect effect mediated through improvement of sleep.
Menopause-the Journal of The North American Menopause Society, 2006
Estrogen therapy (ET) seems to differentially effect cognitive processes in younger versus older ... more Estrogen therapy (ET) seems to differentially effect cognitive processes in younger versus older postmenopausal women, suggesting a window of opportunity when ET is most beneficial. Cognitive improvement in younger postmenopausal women has been attributed to ET's influence on hot flushes and sleep, but empiric examination of the mediating role of menopause symptoms versus direct effects of ET on the brain is limited. In a double-blind trial, 52 women were randomly assigned to estradiol 0.05 mg/day (n = 26) or placebo transdermal patches (n = 26) for 12 weeks. Women completed tests of memory, learning, and executive functioning, and hot flush and sleep assessments at baseline and study end. A subset of women (five ET treated, six placebo treated) also underwent blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies. Nondepressed perimenopausal and postmenopausal women were studied. The majority had hot flushes and sleep impairment. Compared with placebo, ET selectively reduced errors of perseveration during verbal recall (P = 0.03), a frontal system-mediated function, but did not influence other cognitive processes. Women with baseline hot flushes had greater cognitive benefit with ET (P < 0.05). Cognitive benefit was not associated with sleep problems or its improvement. Measures of fMRI BOLD activation during tests of verbal and spatial working memory showed significant increases in frontal system activity with ET (P < 0.001). Estrogen therapy selectively improves executive functioning as demonstrated by reduced perseverative errors and prefrontal cortex activation during verbal recall tasks. Cognitive improvement with ET is associated with hot flushes, but not with sleep, suggesting that ET has a direct central nervous system effect, rather than an indirect effect mediated through improvement of sleep.
... Ranga Reddy Dr.,; Evelyne Dietrich,; Yanick Lafontaine,; Tom J. Houghton Dr.,; Odette Belange... more ... Ranga Reddy Dr.,; Evelyne Dietrich,; Yanick Lafontaine,; Tom J. Houghton Dr.,; Odette Belanger,; Anik Dubois,; Francis F. Arhin Dr.,; Ingrid Sarmiento,; Ibtihal Fadhil,; Karine Laquerre,; Valerie Ostiguy,; Dario Lehoux Dr.,; Gregory Moeck Dr.,; Thomas R. Parr Jr. Dr.,; Adel Rafai Far ...
Screening of a chemical library in a DNA helicase assay involving the Pseudomonas aeruginosa DnaB... more Screening of a chemical library in a DNA helicase assay involving the Pseudomonas aeruginosa DnaB helicase provided a triaminotriazine inhibitor with good antibacterial activity but associated cytotoxicity toward mammalian cells. Synthesis of analogs provided a few inhibitors that retained antibacterial activity and demonstrated a significant reduction in cytotoxicity. The impact of serum and initial investigations toward a mode of action highlight several features of this class of compounds as antibacterials.The structure–activity relationships around a Pseudomonas aeruginosa DNA helicase triaminotriazine inhibitor in terms of inhibitory and antibacterial activities as well as cytotoxicity toward mammalian cells are presented. Several features of this class of compounds as antibacterials are highlighted.
Oritavancin is a lipoglycopeptide with activity against gram-positive pathogens including vancomy... more Oritavancin is a lipoglycopeptide with activity against gram-positive pathogens including vancomycin-resistant enterococci. The impact of human serum albumin (HSA) on oritavancin activity against enterococci was compared to those of vancomycin, daptomycin, teicoplanin, and linezolid in vitro using MIC and time-kill methods. Oritavancin MICs increased between 0- and 8-fold in the presence of HSA. In time-kill assays with HSA, oritavancin retained activity, killing or inhibiting enterococci more rapidly than did comparators when peak concentrations were simulated.
To determine if S-adenosyl-L-methionine (SAMe), a widely used dietary supplement with antidepress... more To determine if S-adenosyl-L-methionine (SAMe), a widely used dietary supplement with antidepressant properties, is significantly bioavailable, and whether toxic methylated compounds are produced with oral SAMe administration in humans. Serum homocysteine levels were also measured since alterations in these levels have been theorized in association with SAMe. Unblinded pharmacokinetic trial. Fifteen healthy volunteers. Clinical research unit in a psychiatric hospital. Subjects received oral SAMe for 4 weeks; the dosage was titrated over 5 days to 1600 mg/day. Serum levels of SAMe, toxic methylated compounds (methanol, formaldehyde, and formic acid), and homocysteine were measured at baseline and at weeks 2 and 4. At baseline, a structured clinical interview for axis I disorders (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) was completed to assess for any undiagnosed psychiatric disorders. Mood was rated at baseline and at weeks 2 and 4 using the Zung Depression Rating Scale, Young Mania Rating Scale, Montgomery-Asberg Depression Rating Scale, Clinical Global Impression Scale, and the Global Assessment of Function Scale. After oral administration, SAMe levels were significantly elevated. Slight, likely insignificant, elevations in serum formaldehyde levels were detected in three subjects. No subject exhibited elevated homocysteine levels during SAMe treatment. One subject developed a transient mixed manic state with suicidal ideation within 2 weeks of starting SAMe; she recovered fully within 3 days of discontinuing the compound. Oral dosages of 1600 mg/day of SAMe appear to be significantly bioavailable and nontoxic, at least regarding toxic methylated metabolites and homocysteine. However, the risk of mania in vulnerable individuals remains a serious concern.
Diagnostic Microbiology and Infectious Disease, 2009
Human serum albumin (HSA) did not affect oritavancin MICs against non–vancomycin-intermediate Sta... more Human serum albumin (HSA) did not affect oritavancin MICs against non–vancomycin-intermediate Staphylococcus aureus (non-VISA) strains. In time–kill assays, oritavancin bactericidal activity in the presence of HSA was significantly more rapid than comparators against non-VISA strains. HSA increased oritavancin MICs by 4-fold for VISA strains, reflective of reduced oritavancin activity in time–kill assays with HSA.
Osteomyelitis is an infection located in bone and a notoriously difficult disease to manage, requ... more Osteomyelitis is an infection located in bone and a notoriously difficult disease to manage, requiring frequent and heavy doses of systemically administered antibiotics. Targeting antibiotics to the bone after systemic administration may provide both greater efficacy of treatment and less frequent administration. By taking advantage of the affinity of the bisphosphonate group for bone mineral, we have prepared a set of 13 bisphosphonated antibacterial prodrugs based on eight different linkers tethered to the free amino functionality on fluoroquinolone antibiotics. While all but one of the prodrugs were shown in vitro to be effective and rapid bone binders (over 90% in 1 h), only eight of them demonstrated the capacity to significantly regenerate the parent drug. In a rat model of the disease, a selected group of agents demonstrated their ability to prevent osteomyelitis when used in circumstances under which the parent drug had already been cleared and is thus inactive.
Although extensive research has found a strong relationship between poor family functioning and d... more Although extensive research has found a strong relationship between poor family functioning and depression, previous research has not examined this relationship among low-income Latinos. In this study, we examined how family functioning may be associated with depression in a sample of low-income Latino couples. In addition, we examined how acculturative stress moderates the relationship between family functioning and depression. Our results indicate that the relationship between family functioning and depression is stronger in women and that acculturative stress moderates this relationship in women. Probing this interaction indicates that women who reported high acculturative stress coupled with poor family functioning experienced more depression. Clinical implications are discussed.
This paper describes the experiences of the first author and his colleagues in the development an... more This paper describes the experiences of the first author and his colleagues in the development and implementation of a depression prevention program that specifically targets Latina mothers. Building on the earlier papers that highlight the underutilization of mental health services by Latinos in general, this paper will make the case that the situation is particularly concerning with regards to depression. In addition to the fact that depression is a highly prevalent disorder among Latino adults, the potential consequences for children of parents with depression are significant. Thus, the underutilization of formal mental health services by Latinos makes depression a critical public health problem that calls for creative solutions. One possible solution is the careful development and implementation of prevention programs. Depression prevention programs have some advantages over formal mental health treatment in that they can be offered at a relatively low cost, can be packaged in ways that make them less stigmatizing, and if effective, can reduce the incidence of cases that develop into clinical depression.This paper will describe the process of developing a novel depression prevention program, with a particular focus on the attention paid to cultural sensitivity. We describe the complexity inherent in defining cultural sensitivity and illustrate in concrete ways its implementation in the development and evaluation of the prevention program. In addition, we explore some of the challenges that emerge when attempting to balance the creation of a program that is culturally sensitive with the demands of rigorous quantitative evaluation.
Estrogen therapy (ET) seems to differentially effect cognitive processes in younger versus older ... more Estrogen therapy (ET) seems to differentially effect cognitive processes in younger versus older postmenopausal women, suggesting a window of opportunity when ET is most beneficial. Cognitive improvement in younger postmenopausal women has been attributed to ET's influence on hot flushes and sleep, but empiric examination of the mediating role of menopause symptoms versus direct effects of ET on the brain is limited. In a double-blind trial, 52 women were randomly assigned to estradiol 0.05 mg/day (n = 26) or placebo transdermal patches (n = 26) for 12 weeks. Women completed tests of memory, learning, and executive functioning, and hot flush and sleep assessments at baseline and study end. A subset of women (five ET treated, six placebo treated) also underwent blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies. Nondepressed perimenopausal and postmenopausal women were studied. The majority had hot flushes and sleep impairment. Compared with placebo, ET selectively reduced errors of perseveration during verbal recall (P = 0.03), a frontal system-mediated function, but did not influence other cognitive processes. Women with baseline hot flushes had greater cognitive benefit with ET (P < 0.05). Cognitive benefit was not associated with sleep problems or its improvement. Measures of fMRI BOLD activation during tests of verbal and spatial working memory showed significant increases in frontal system activity with ET (P < 0.001). Estrogen therapy selectively improves executive functioning as demonstrated by reduced perseverative errors and prefrontal cortex activation during verbal recall tasks. Cognitive improvement with ET is associated with hot flushes, but not with sleep, suggesting that ET has a direct central nervous system effect, rather than an indirect effect mediated through improvement of sleep.
Menopause-the Journal of The North American Menopause Society, 2006
Estrogen therapy (ET) seems to differentially effect cognitive processes in younger versus older ... more Estrogen therapy (ET) seems to differentially effect cognitive processes in younger versus older postmenopausal women, suggesting a window of opportunity when ET is most beneficial. Cognitive improvement in younger postmenopausal women has been attributed to ET's influence on hot flushes and sleep, but empiric examination of the mediating role of menopause symptoms versus direct effects of ET on the brain is limited. In a double-blind trial, 52 women were randomly assigned to estradiol 0.05 mg/day (n = 26) or placebo transdermal patches (n = 26) for 12 weeks. Women completed tests of memory, learning, and executive functioning, and hot flush and sleep assessments at baseline and study end. A subset of women (five ET treated, six placebo treated) also underwent blood oxygenation level-dependent (BOLD) functional magnetic resonance imaging (fMRI) studies. Nondepressed perimenopausal and postmenopausal women were studied. The majority had hot flushes and sleep impairment. Compared with placebo, ET selectively reduced errors of perseveration during verbal recall (P = 0.03), a frontal system-mediated function, but did not influence other cognitive processes. Women with baseline hot flushes had greater cognitive benefit with ET (P < 0.05). Cognitive benefit was not associated with sleep problems or its improvement. Measures of fMRI BOLD activation during tests of verbal and spatial working memory showed significant increases in frontal system activity with ET (P < 0.001). Estrogen therapy selectively improves executive functioning as demonstrated by reduced perseverative errors and prefrontal cortex activation during verbal recall tasks. Cognitive improvement with ET is associated with hot flushes, but not with sleep, suggesting that ET has a direct central nervous system effect, rather than an indirect effect mediated through improvement of sleep.
... Ranga Reddy Dr.,; Evelyne Dietrich,; Yanick Lafontaine,; Tom J. Houghton Dr.,; Odette Belange... more ... Ranga Reddy Dr.,; Evelyne Dietrich,; Yanick Lafontaine,; Tom J. Houghton Dr.,; Odette Belanger,; Anik Dubois,; Francis F. Arhin Dr.,; Ingrid Sarmiento,; Ibtihal Fadhil,; Karine Laquerre,; Valerie Ostiguy,; Dario Lehoux Dr.,; Gregory Moeck Dr.,; Thomas R. Parr Jr. Dr.,; Adel Rafai Far ...
Screening of a chemical library in a DNA helicase assay involving the Pseudomonas aeruginosa DnaB... more Screening of a chemical library in a DNA helicase assay involving the Pseudomonas aeruginosa DnaB helicase provided a triaminotriazine inhibitor with good antibacterial activity but associated cytotoxicity toward mammalian cells. Synthesis of analogs provided a few inhibitors that retained antibacterial activity and demonstrated a significant reduction in cytotoxicity. The impact of serum and initial investigations toward a mode of action highlight several features of this class of compounds as antibacterials.The structure–activity relationships around a Pseudomonas aeruginosa DNA helicase triaminotriazine inhibitor in terms of inhibitory and antibacterial activities as well as cytotoxicity toward mammalian cells are presented. Several features of this class of compounds as antibacterials are highlighted.
Oritavancin is a lipoglycopeptide with activity against gram-positive pathogens including vancomy... more Oritavancin is a lipoglycopeptide with activity against gram-positive pathogens including vancomycin-resistant enterococci. The impact of human serum albumin (HSA) on oritavancin activity against enterococci was compared to those of vancomycin, daptomycin, teicoplanin, and linezolid in vitro using MIC and time-kill methods. Oritavancin MICs increased between 0- and 8-fold in the presence of HSA. In time-kill assays with HSA, oritavancin retained activity, killing or inhibiting enterococci more rapidly than did comparators when peak concentrations were simulated.
To determine if S-adenosyl-L-methionine (SAMe), a widely used dietary supplement with antidepress... more To determine if S-adenosyl-L-methionine (SAMe), a widely used dietary supplement with antidepressant properties, is significantly bioavailable, and whether toxic methylated compounds are produced with oral SAMe administration in humans. Serum homocysteine levels were also measured since alterations in these levels have been theorized in association with SAMe. Unblinded pharmacokinetic trial. Fifteen healthy volunteers. Clinical research unit in a psychiatric hospital. Subjects received oral SAMe for 4 weeks; the dosage was titrated over 5 days to 1600 mg/day. Serum levels of SAMe, toxic methylated compounds (methanol, formaldehyde, and formic acid), and homocysteine were measured at baseline and at weeks 2 and 4. At baseline, a structured clinical interview for axis I disorders (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition) was completed to assess for any undiagnosed psychiatric disorders. Mood was rated at baseline and at weeks 2 and 4 using the Zung Depression Rating Scale, Young Mania Rating Scale, Montgomery-Asberg Depression Rating Scale, Clinical Global Impression Scale, and the Global Assessment of Function Scale. After oral administration, SAMe levels were significantly elevated. Slight, likely insignificant, elevations in serum formaldehyde levels were detected in three subjects. No subject exhibited elevated homocysteine levels during SAMe treatment. One subject developed a transient mixed manic state with suicidal ideation within 2 weeks of starting SAMe; she recovered fully within 3 days of discontinuing the compound. Oral dosages of 1600 mg/day of SAMe appear to be significantly bioavailable and nontoxic, at least regarding toxic methylated metabolites and homocysteine. However, the risk of mania in vulnerable individuals remains a serious concern.
Diagnostic Microbiology and Infectious Disease, 2009
Human serum albumin (HSA) did not affect oritavancin MICs against non–vancomycin-intermediate Sta... more Human serum albumin (HSA) did not affect oritavancin MICs against non–vancomycin-intermediate Staphylococcus aureus (non-VISA) strains. In time–kill assays, oritavancin bactericidal activity in the presence of HSA was significantly more rapid than comparators against non-VISA strains. HSA increased oritavancin MICs by 4-fold for VISA strains, reflective of reduced oritavancin activity in time–kill assays with HSA.
Osteomyelitis is an infection located in bone and a notoriously difficult disease to manage, requ... more Osteomyelitis is an infection located in bone and a notoriously difficult disease to manage, requiring frequent and heavy doses of systemically administered antibiotics. Targeting antibiotics to the bone after systemic administration may provide both greater efficacy of treatment and less frequent administration. By taking advantage of the affinity of the bisphosphonate group for bone mineral, we have prepared a set of 13 bisphosphonated antibacterial prodrugs based on eight different linkers tethered to the free amino functionality on fluoroquinolone antibiotics. While all but one of the prodrugs were shown in vitro to be effective and rapid bone binders (over 90% in 1 h), only eight of them demonstrated the capacity to significantly regenerate the parent drug. In a rat model of the disease, a selected group of agents demonstrated their ability to prevent osteomyelitis when used in circumstances under which the parent drug had already been cleared and is thus inactive.
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