Crisis leadership: a case for inclusion in accredited Master of Public Health program curricula.

OBJECTIVES: To evaluate the exposure to crisis leadership theory already present in Council on Education for Public Health (CEPH) accredited Master of Public Health (MPH) programs in the United States and provide a compelling case for its future inclusion. STUDY DESIGN: This was a narrative review. METHODS: We compiled a comprehensive list of 179 CEPH schools that offered an MPH program. During January through March 2021, we examined 179 websites for the core courses and elective courses offered in the MPH degree program to determine if any courses covered the topics of leadership, crisis leadership, or crisis management in either the course title or description. RESULTS: Leadership courses were available in only 55.31% of CEPH-accredited schools. Only a single program (0.56%) offers a crisis leadership course. CONCLUSIONS: The current global COVID-19 pandemic and reality of climate-induced disasters have brought crises to the forefront for health systems. Successful leadership for the future requires public health leaders to have training in crisis leadership. The evaluation and revision of public health curricula must focus on leadership competency development to prepare graduates to lead complex multiple crisis events and system shocks simultaneously.

Coinfections identified from metagenomic analysis of cervical lymph nodes from tularemia patients.

BACKGROUND: Underlying coinfections may complicate infectious disease states but commonly go unnoticed because an a priori clinical suspicion is usually required so they can be detected via targeted diagnostic tools. Shotgun metagenomics is a broad diagnostic tool that can be useful for identifying multiple microbes simultaneously especially if coupled with lymph node aspirates, a clinical matrix known to house disparate pathogens. The objective of this study was to analyze the utility of this unconventional diagnostic approach (shotgun metagenomics) using clinical samples from human tularemia cases as a test model. Tularemia, caused by the bacterium Francisella tularensis, is an emerging infectious disease in Turkey. This disease commonly manifests as swelling of the lymph nodes nearest to the entry of infection. Because swollen cervical nodes are observed from many different types of human infections we used these clinical sample types to analyze the utility of shotgun metagenomics. METHODS: We conducted an unbiased molecular survey using shotgun metagenomics sequencing of DNA extracts from fine-needle aspirates of neck lymph nodes from eight tularemia patients who displayed protracted symptoms. The resulting metagenomics data were searched for microbial sequences (bacterial and viral). RESULTS: F. tularensis sequences were detected in all samples. In addition, we detected DNA of other known pathogens in three patients. Both Hepatitis B virus (HBV) and Human Parvovirus B-19 were detected in one individual and Human Parvovirus B-19 alone was detected in two other individuals. Subsequent PCR coupled with Sanger sequencing verified the metagenomics results. The HBV status was independently confirmed via serological diagnostics, despite evading notice during the initial assessment. CONCLUSION: Our data highlight that shotgun metagenomics of fine-needle lymph node aspirates is a promising clinical diagnostic strategy to identify coinfections. Given the feasibility of the diagnostic approach demonstrated here, further steps to promote integration of this type of diagnostic capability into mainstream clinical practice are warranted.

Addiction potential of phentermine prescribed during long-term treatment of obesity.

OBJECTIVE: To investigate if phentermine treatment induces phentermine abuse, psychological dependence (addiction) or phentermine drug craving in overweight, obese and weight loss maintenance patients. To investigate whether amphetamine-like withdrawal occurs after abrupt cessation of long-term phentermine treatment. DESIGN: Clinical intervention trial with interruption of phentermine treatment in long-term patients. SUBJECTS: 269 obese, overweight or formerly obese subjects (age: 20-88 years, BMI: 21-74 kg m(-2)) treated with phentermine long-term (LTP, N=117), 1.1-21.1 years, or short-term (ATP, N=152), 4-22 days, with phentermine doses of 18.75-112.5 (LTP) and 15-93.75 (ATP) mg per day. MEASUREMENTS: Module K of the Mini International Neuropsychiatric Interview modified for phentermine (MINI-SUD), Severity of Dependence Scale (SDS), 45-item Cocaine Craving Questionnaire-NOW (CCQ-NOW) modified for phentermine (PCQ-NOW), and Amphetamine Withdrawal Questionnaire (AWQ) modified for phentermine (PWQ). RESULTS: MINI-SUD interviews were negative for phentermine abuse or psychological dependence in all LTP patients. SDS examination scores were low for all LTP and ATP patients, indicating they were not psychologically dependent upon phentermine. PCQ-NOW scores were low for all LTP and ATP patients, indicating neither short-term nor long-term phentermine treatment had induced phentermine craving. Other than an increase in hunger or eating, amphetamine-like withdrawal symptoms did not occur upon abrupt phentermine cessation as measured by sequential PWQ scores. CONCLUSIONS: Phentermine abuse or psychological dependence (addiction) does not occur in patients treated with phentermine for obesity. Phentermine treatment does not induce phentermine drug craving, a hallmark sign of addiction. Amphetamine-like withdrawal does not occur upon abrupt treatment cessation even at doses much higher than commonly recommended and after treatment durations of up to 21 years.

Identification of early predictive imaging biomarkers and their relationship to serological angiogenic markers in patients with ovarian cancer with residual disease following cytotoxic therapy.

BACKGROUND: Patients with recurrent ovarian cancer often achieve partial response following chemotherapy, resulting in persistent small volume disease. After completion of treatment, the dilemma of when to initiate subsequent chemotherapy arises. Identification of biomarkers that could be used to predict when subsequent treatment is needed would be of significant benefit. DESIGN: Twenty-three patients with advanced ovarian cancer and residual asymptomatic disease following chemotherapy underwent dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) at study entry, 4, 8, 12, 18 and 26 weeks or disease progression. A subgroup of patients provided plasma samples within which a panel of angiogenic biomarkers was quantified. RESULTS: By 4 weeks, significant differences in whole tumour volume, enhancing fraction and Ca125 were observed between patients whose disease progressed by 26 weeks and those who remained stable. Significant correlations between plasma soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) and sVEGFR-2 concentrations, and blood volume and tumour endothelial permeability surface area product measured by DCE-MRI were observed. CONCLUSIONS: Imaging markers have a potential role in early prediction of disease progression in patients with residual ovarian cancer and may supplement current measures of progression. The correlation of DCE-MRI and serological biomarkers suggests that tumour angiogenesis affects these markers through common biological means and warrants further investigation.

New FACTOR IX linked marker alleles in African Haemophilia B patients.

Three markers, one restriction length polymorphism (RFLP) (MseI) and two microsatellite markers (Intron 1 and 3'UTR), linked to the FACTOR IX gene, were assessed for the purpose of genetic testing for Haemophilia B families in South Africa. This was carried out using seven Haemophilia B families and fifty random control samples. We observed five new alleles for the Intron 1 marker within the black control and patient sample groups, and informativity in 89% (8/9) of all carrier females for at least one of the three markers observed. These markers are useful for carrier detection and prenatal diagnosis of Haemophilia B in the great majority of South African black and white families.

The infant with primary hyperoxaluria and oxalosis: from diagnosis to multiorgan transplantation.

The care of an infant with primary hyperoxaluria and oxalosis is discussed. After an unheralded presentation, followed by 9 months of intensive treatment that included combined hemodialysis and peritoneal dialysis, the infant successfully underwent combined liver and kidney transplantation to definitely address both kidney failure and the underlying metabolic defect. Discussion of this approach, including ongoing input from the parents, addresses both the implications of undertaking the "best therapy" for this disease as well as the ethical dilemma passed by the decision whether to proceed or not to proceed with therapy.

The economic impact of hurricane Hugo on the Eastern Caribbean

The Eastern Caribbean region is in the path of tropical storms and hurricanes (depressions) which form in the northeast Atlantic and which move through this region before being drawn up by the warm land mass of the continetal United States. This paper attempts to 1- Examine the economic impact of hurricane Hugo on the Eastern caribbean, specifically its impact on organisation of Eastern Caribbean States (OECS) member states, five of which were hit by this hurricane - Dominica, Montserrat, St. Kitts-Nevis, Antigua-Barbuda and the BVI. 2- Analyse the impact of hurricane planning and mitigation measures in Motserrat, the hardest hit OECS member state and in St. Kitts-Nevis. 3- Draw certain conclusions, and the consequent policy implications from the experiences of these two member states with respect to their planning and mitigation measures (AU)

Chelation of zinc by diethyldithiocarbamate facilitates bursting induced by mixed antidromic plus orthodromic activation of mossy fibers in hippocampal slices.

The effect of chelation of zinc by diethyldithiocarbamate (DEDTC) on bursting of CA3 pyramidal cells induced by mixed antidromic plus orthodromic activation of mossy fibers (MP) in hippocampal slices was studied. Slices perfused in artificial cerebrospinal fluid (ACSF) with high (2.5 mM) Ca2+ rarely exhibited triggered bursting following a series of stimulus trains similar to those used in kindling. In contrast, slices perfused with DEDTC (0.1 mM) in ACSF and subsequently perfused with ACSF alone prior to initiating the stimulus trains exhibited robust triggered bursting following the stimulus trains. However, if slices perfused with ACSF containing DEDTC were then perfused with ACSF containing zinc chloride (0.5 microM) followed by ACSF alone, triggered bursting was not induced subsequent to delivering stimulus trains. It is concluded that release of zinc from the mossy fibers induced by tetanic stimulation serves to obtund bursting in CA3 pyramidal cells.

Proconvulsant action of diethyldithiocarbamate in stimulation of the perforant path.

The ability of diethyldithiocarbamate (DEDTC) to prolong electrical afterdischarge (AD) and lower the threshold for behavioral seizures elicited by stimulation of the perforant path (PPS) was examined. DEDTC was given in doses of 25, 50, and 100 mg/kg, IP. The effects of DEDTC on the threshold for wet dog shakes (WDS) and the number of WDS elicited by PPS were inconsistent. It had no effect on the duration of AD accompanied with WDS. However, DEDTC, at both 50 and 100 mg/kg, significantly lowered the threshold for rearing accompanied with forelimb clonus. At 100 mg/kg, it also prolonged the duration of AD occurring with these seizures. The effects of DEDTC were transitory and coincided with the time course for its ability to chelate the mossy fiber intravesicular pool of zinc (i.e., that which is released by activation of dentate granule cells). It is suggested that release of zinc from the mossy fibers may serve to protect the hippocampus from paroxysmal seizure activity.

Decreased seizure threshold after intrahippocampal colchicine injection in rats.

Wet dog shaking elicited by perforant path stimulation is little affected by bilateral injection of colchicine into the dorsal hippocampal formation but virtually eliminated by bilateral injection into the ventral hippocampal formation. Injection of colchicine into either dorsal or ventral hippocampal formation lowers the threshold for eliciting forelimb clonus with rearing. This effect is more pronounced 8 weeks postinjection than 2 weeks postinjection when colchicine is injected in the ventral hippocampal formation. This suggests that inappropriate reactive synaptogenesis and/or neuronal degeneration continues for an extended period after intrahippocampal injection of colchicine, especially in the ventral hippocampal formation.

Effect of destruction of dentate granule cells on kindling induced by stimulation of the perforant path.

Bilateral destruction of dentate granule cells in both the dorsal and ventral hippocampal formation had no effect on the threshold for hippocampal afterdischarge before or after kindling. Neither did it affect the number of stimulations required to attain kindling. However, the duration of afterdischarge was significantly longer in colchicine-lesioned animals compared to those receiving artificial cerebrospinal fluid. This was true for the threshold for afterdischarge as well as at the first and last kindling trials. These results suggest that dentate granule cells may inhibit the duration of afterdischarge induced by perforant path stimulation or that other postlesion changes occur which result in a prolongation of hippocampal afterdischarge.

A glutamate antagonist blocks perforant path stimulation-induced reduction of dynorphin peptide and prodynorphin mRNA levels in rat hippocampus.

Stimulation of the perforant path elicits a behavioral response, wet dog shakes (WDS), and reduction in hippocampal dynorphin A(1-8) immunoreactivity (DYN-IR) and prodynorphin mRNA (DYN mRNA) in rats. This study examined whether glutamate, the proposed endogenous transmitter released by perforant fibers, mediated the above responses. A glutamate antagonist, gamma-D-glutamylglycine (DGG, 25 micrograms/0.5 microliters), or artificial cerebrospinal fluid (ACSF, 0.5 microliters) was injected into the ventral hippocampus 10-20 min prior to acute or daily stimulation of the left perforant path in rats. In acute stimulation experiments, 4 consecutive stimulation trials elicited a total of 73 +/- 4 WDS at an average threshold intensity of 0.46 +/- 0.03 mA in ACSF-treated rats. The hippocampal DYN-IR in these animals decreased by more than 40% in both dorsal and ventral hippocampus relative to sham-stimulated rats. DGG injections significantly elevated the threshold for WDS (0.78 +/- 0.05 mA, P less than 0.01), reduced the number of WDS (45 +/- 6, P less than 0.01), and partially antagonized stimulation-induced reduction of DYN-IR in the ventral, but not dorsal, hippocampus. In daily stimulation experiments, rats received a single trial of stimulation once per day for 6 days. Daily DGG pretreatment almost completely abolished WDS at control threshold intensities, and significantly inhibited stimulation-induced decrease of DYN-IR in both dorsal and ventral hippocampus. In situ hybridization using a 35S-labeled oligodeoxyribonucleotide probe demonstrated a clear depletion of DYN mRNA signal in the dentate granule cell layer of ACSF-treated animals. This depletion was completely prevented in DGG-treated rats.(ABSTRACT TRUNCATED AT 250 WORDS)

Opioid mu and delta receptor antagonists reduce wet dog shaking elicited by perforant path stimulation.

Stimulation of the perforant path, a major input to the hippocampal formation, produced significant decreases in the hippocampal levels of methionine enkephalin, dynorphin A(1-8) and an increase in the hippocampal level of gamma-aminobutyric acid. In addition, it was also observed that both mu and delta opioid receptor antagonists reduce wet dog shakes elicited by perforant path stimulation. The antagonists did not affect the changes in hippocampal levels of methionine enkephalin, dynorphin A(1-8) or gamma-aminobutyric acid. The results demonstrate that endogenous opioids are involved in the wet dog shakes elicited by perforant path stimulation. Since electrographic seizure activity occurs in the hippocampus in conjunction with perforant path stimulation-induced wet dog shakes, these data provide further evidence that endogenous opioid peptides play an important role in regulation of limbic system epileptogenic phenomena.

Differential effects of colchicine lesions of dentate granule cells on wet dog shakes and seizures elicited by direct hippocampal stimulation.

Direct electrical stimulation of either the dorsal or ventral hippocampal formation elicits wet dog shakes and overt seizures. Destruction of dentate granule cells in the dorsal hippocampal formation does not significantly reduce the number of wet dog shakes elicited by ventral hippocampal stimulation. However, destruction of dentate granule cells in the ventral hippocampus virtually eliminates wet dog shaking elicited by dorsal hippocampal stimulation. Destruction of either dorsal or ventral dentate granule cells lowers the threshold for eliciting forelimb clonus with rearing. These results suggest that dentate granule cells in the ventral hippocampus are essential for wet dog shakes elicited by intrahippocampal stimulation. However, dentate granule cells throughout the hippocampal formation appear to play an important inhibitory role in the spread of seizure activity within the hippocampus.

Opioid-induced epileptiform bursting in hippocampal slices: higher susceptibility in ventral than dorsal hippocampus.

The disparity between the seizure sensitivity of the dorsal and ventral hippocampus to opioid peptides was studied by an in vitro electrophysiological method. Slices taken from the ventral (temporal) and dorsal (septal) regions of rat hippocampi were perfused in artificial cerebrospinal fluid bubbled continuously with 95% O2-5% CO2 at 34 degrees C. A stimulating electrode was placed in the stratum radiatum of CA3 region and electrical activity was recorded from the pyramidal cell body layer of the CA3b region. Paired dorsal and ventral hippocampal slices were perfused with [N-Me-Phe3-D-Pro4]morphiceptin (PL017), a specific mu opioid receptor agonist. Application of 0.05 microM PL017 produced triggered and spontaneous bursting in 20% of ventral hippocampal slices, but no such effect was observed in dorsal hippocampal slices. At 0.5 microM PL017, 80% of ventral hippocampal slices developed spontaneous bursting, whereas only 10% of dorsal hippocampal slices had spontaneous bursting. Slices from the ventral hippocampus consistently produced greater degrees of bursting at lower doses relative to the dorsal hippocampus. The addition of 0.1 microM naloxone before or after PL017 inhibited the triggered response but could not block the spontaneous bursting. Perfusion of ACSF for 1 hr also eliminated the triggered response but could only reduce the frequency of the spontaneous bursting. These results suggest that the ventral hippocampus has a higher susceptibility to PL017-induced epileptiform bursting, and this effect is mediated, at least in part, through mu opioid receptors.

Granule cells in the ventral, but not dorsal, dentate gyrus are essential for kainic acid-induced wet dog shakes.

Intrahippocampal injections of colchicine selectively destroy dentate granule cells. Wet dog shaking elicited by systemic administration of kainic acid is eliminated by bilateral destruction of ventral dentate granule cells but unaffected by bilateral destruction of dorsal dentate granule cells. This implies that ventral dentate granule cells are essential for the generation of kainic acid-induced wet dog shakes.

Perforant path stimulation differentially alters prodynorphin mRNA and proenkephalin mRNA levels in the entorhinal cortex-hippocampal region.

The regulatory effect of the perforant path on opioid gene expression in the entorhinal cortex-hippocampal region was investigated. The left perforant path was electrically stimulated at the angular bundle under conditions which elicit wet dog shakes but no motor seizures in rats. Animals were given either an acute stimulation composed of several consecutive stimulation trials, or daily stimulations with a single trial every day for 6 days. Rats were then sacrificed at 24 h or 6 days after the last trial. The amounts of prodynorphin mRNA (DYN mRNA) and proenkephalin A mRNA (EK mRNA) in the hippocampus and entorhinal cortex were measured by RNA blot analysis. Dynorphin A(1-8) and [Met5]enkephalin immunoreactivities were determined by radioimmunoassay. A decrease in DYN mRNA level of approximately 50-80% was found on both sides of the hippocampus 24 h after both acute and daily stimulation. Hippocampal dynorphin A(1-8) immunoreactivity was also reduced at 24 h, and persisted for at least 6 days. In contrast, bilateral increases in EK mRNA level were observed in the hippocampus (54-101%) and entorhinal cortex (97-165%) 24 h after the acute stimulation. Also, [Met5]enkephalin immunoreactivity in the hippocampus tended to be increased at this time. These results indicate that activation of the perforant path inhibits the gene expression of prodynorphin, but enhances that of proenkephalin in the entorhinal cortex-hippocampal region.

Granule cells in the ventral dentate gyrus are essential for kainic acid-induced wet dog shakes but not those induced by precipitated abstinence in morphine-dependent rats.

Wet dog shaking elicited by systemic administration of kainic acid is eliminated by bilateral destruction of ventral dentate granule cells. In contrast, wet dog shaking induced by naltrexone precipitated abstinence in morphine-dependent rats is unaffected by destruction of ventral dentate granule cells. It is concluded that at least two anatomically distinct brain regions modulate wet dog shaking behavior.

Colchicine lesions of ventral, but not dorsal, dentate granule cells attenuate wet dog shakes elicited by perforant path stimulation.

Intrahippocampal injections of colchicine selectively destroy dentate granule cells. Wet dog shaking elicited by perforant path stimulation is unaffected by bilateral destruction of dorsal dentate granule cells but virtually eliminated by bilateral destruction of ventral dentate granule cells. This implies that ventral dentate granule cells are essential for the generation of perforant path stimulation-induced wet dog shakes.