Ultra-low pressure hydrocephalic state in NPH: benefits of therapeutic siphoning with adjustable anti-gravity valves

Background: Idiopathic normal-pressure hydrocephalus (NPH) is a condition of the elderly treated by ventriculoperitoneal shunt (VP) insertion. A subset of NPH patients respond only temporarily to shunt insertion despite low valve opening pressure. This study aims to describe our experience of patients who benefit from further CSF drainage by adding adjustable antigravity valves and draining CSF at ultra-low pressure. Methods: Single-centre retrospective case series of patients undergoing shunt valve revision from an adjustable differential pressure valve with fixed antigravity unit to a system incorporating an adjustable gravitational valve (Miethke proSA). Patients were screened from a database of NPH patients undergoing CSF diversion over 10 consecutive years (April 2008–April 2018). Clinical records were retrospectively reviewed for interventions and clinical outcomes. Results Nineteen (10F:9M) patients underwent elective VP shunt revision to a system incorporating an adjustable gravitational valve. Mean age 77.1 ± 7.1 years (mean ± SD). Eleven patients (58%) showed significant improvement in walking speed following shunt revision. Fourteen patients/carers (74%) reported subjective improvements in symptoms following shunt revision. Conclusions: Patients presenting symptoms relapse following VP shunting may represent a group of patients with ultra-low-pressure hydrocephalus, for whom further CSF drainage may lead to an improvement in symptoms. These cases may benefit from shunt revision with an adjustable gravitational valve, adjustment of which can lead to controlled siphoning of CSF and drain CSF despite ultra-low CSF pressure

Lipidomics Reveals Early Metabolic Changes in Subjects with Schizophrenia: Effects of Atypical Antipsychotics

There is a critical need for mapping early metabolic changes in schizophrenia to capture failures in regulation of biochemical pathways and networks. This information could provide valuable insights about disease mechanisms, trajectory of disease progression, and diagnostic biomarkers. We used a lipidomics platform to measure individual lipid species in 20 drug-naïve patients with a first episode of schizophrenia (FE group), 20 patients with chronic schizophrenia that had not adhered to prescribed medications (RE group), and 29 race-matched control subjects without schizophrenia. Lipid metabolic profiles were evaluated and compared between study groups and within groups before and after treatment with atypical antipsychotics, risperidone and aripiprazole. Finally, we mapped lipid profiles to n3 and n6 fatty acid synthesis pathways to elucidate which enzymes might be affected by disease and treatment. Compared to controls, the FE group showed significant down-regulation of several n3 polyunsaturated fatty acids (PUFAs), including 20:5n3, 22:5n3, and 22:6n3 within the phosphatidylcholine and phosphatidylethanolamine lipid classes. Differences between FE and controls were only observed in the n3 class PUFAs; no differences where noted in n6 class PUFAs. The RE group was not significantly different from controls, although some compositional differences within PUFAs were noted. Drug treatment was able to correct the aberrant PUFA levels noted in FE patients, but changes in re patients were not corrective. Treatment caused increases in both n3 and n6 class lipids. These results supported the hypothesis that phospholipid n3 fatty acid deficits are present early in the course of schizophrenia and tend not to persist throughout its course. These changes in lipid metabolism could indicate a metabolic vulnerability in patients with schizophrenia that occurs early in development of the disease. © 2013 McEvoy et al

Anti-malarial prescriptions in three health care facilities after the emergence of chloroquine resistance in Niakhar, Senegal (1992–2004)

<p>Abstract</p> <p>Background</p> <p>In the rural zone of Niakhar in Senegal, the first therapeutic failures for chloroquine (CQ) were observed in 1992. In 2003, the national policy regarding first-line treatment of uncomplicated malaria was modified, replacing CQ by a transitory bi-therapy amodiaquine/sulphadoxine-pyrimethamine (AQ/SP), before the implementation of artemisinin-based combination therapy (ACT) in 2006.</p> <p>The aims of the study were to assess the evolution of anti-malarial prescriptions in three health care facilities between 1992 and 2004, in parallel with increasing CQ resistance in the region.</p> <p>Methods</p> <p>The study was conducted in the area of Niakhar, a demographic surveillance site located in a sahelo-sudanese region of Senegal, with mesoendemic and seasonal malaria transmission. Health records of two public health centres and a private catholic dispensary were collected retrospectively to cover the period 1992–2004.</p> <p>Results</p> <p>Records included 110,093 consultations and 292,965 prescribed treatments. Twenty-five percent of treatments were anti-malarials, prescribed to 49% of patients. They were delivered all year long, but especially during the rainy season, and 20% of patients with no clinical malaria diagnosis received anti-malarials. Chloroquine and quinine represented respectively 55.7% and 34.6% of prescribed anti-malarials. Overall, chloroquine prescriptions rose from 1992 to 2000, in parallel with clinical malaria; then the CQ prescription rate decreased from 2000 and was concomitant with the rise of SP and the persistence of quinine use. AQ and SP were mainly used as bi-therapy after 2003, at the time of national treatment policy change.</p> <p>Conclusion</p> <p>The results show the overall level of anti-malarial prescription in the study area for a considerable number of patients over a large period of time. Even though resistance to CQ rapidly increased from 1992 to 2001, no change in CQ prescription was observed until the early 2000s, possibly due to the absence of an obvious decrease in CQ effectiveness, a lack of therapeutic options or a blind follow-up of national guidelines.</p

Effectiveness of guided self-help in decreasing expressed emotion in family caregivers of people diagnosed with depression in Thailand: a randomised controlled trial

Background: High expressed emotion (EE) can extend the duration of illness and precipitate relapse; however, little evidence-based information is available to assist family caregivers of individuals with depression. In the present exploratory study, we examined the effectiveness of a cognitive behaviour therapy (CBT) based guided self-help (GSH) manual in decreasing EE in caregivers of people with depression, in Thailand. Method: A parallel group randomised controlled trial was conducted, following CONSORT guidelines, with 54 caregivers who were allocated equally to GSH or control group (standard outpatient department support). In addition, both groups were contacted weekly by telephone. EE was assessed, using the Family Questionnaire (FQ), at baseline, post-test (Week 8) and follow-up (Week 12). Results: FQ scores at baseline indicated that both groups had similar, though moderately high level of EE. However, between baseline and post-test EE scores decreased markedly in the intervention group, but in contrast, they increased slightly in the control group. Between post-test and follow-up, little change took place in the EE scores of either group. Overall, the intervention group recipients of GSH showed a significant decrease in EE whereas the control group recipients of standard outpatient department support reported a slight increase in EE. Conclusion: These findings provide preliminary evidence that GSH is beneficial in reducing EE in caregivers, which is advantageous to family members with depression and caregivers. The approach may be used as an adjunct to the limited outpatient department support given to caregivers by mental health professionals and, perhaps, to caregivers who do not attend these departments

Intracranial pressure in patients with papilloedema

OBJECTIVES: Papilloedema is a clinical manifestation of chronically raised intracranial pressure (ICP), often seen in idiopathic intracranial hypertension (IIH). However, the extent of intracranial hypertension required to produce papilloedema is not known. We compare ICP values in IIH patients who developed papilloedema and those who did not. We aim to identify a pathological ICP threshold predictive of the development of papilloedema in IIH patients. MATERIALS AND METHODS: Single-centre cohort of IIH patients (2006-2016) who underwent 24-hour ICP monitoring (ICPM) and ophthalmology assessments, prior to intervention. Papilloedema was graded according to the Frisén scale. An unpaired t-test compared 24-hour ICPM between papilloedema and no-papilloedema groups. Fisher's exact test was used to determine predictive value of ICP. RESULTS: Thirty-six patients with IIH (35 F: 1M), mean age 32.5 ± 9.49 years (mean ± SD) were included. Patients with papilloedema had a mean median 24-hour ICP of 10.4 ± 5.32 mm Hg (n = 25), significantly higher than the group without papilloedema 6.31 ± 3.30 mm Hg (n = 11) (P < .05). The papilloedema group were exposed to higher pressures (10 mm Hg) for 30 minutes or more. Using 24-hour median ICP of 10 mm Hg as a minimum cut-off predictive value gives a specificity = 91%, sensitivity = 48%, PPV = 92% and NPV = 44% of detecting papilloedema. CONCLUSIONS: A 24-hour ICP of 10 mmHg or more is a good predictor for papilloedema and reflects a pathological threshold. The range varied widely suggesting papilloedema can occur at even lower pressures. These results are consistent with emerging evidence suggest that pathologically "high" 24 hours ICP is lower than previously quoted

A new hammer to crack an old nut : interspecific competitive resource capture by plants is regulated by nutrient supply, not climate

Peer reviewedPublisher PD

Blocking TLR7- and TLR9-mediated IFN-α Production by Plasmacytoid Dendritic Cells Does Not Diminish Immune Activation in Early SIV Infection

Persistent production of type I interferon (IFN) by activated plasmacytoid dendritic cells (pDC) is a leading model to explain chronic immune activation in human immunodeficiency virus (HIV) infection but direct evidence for this is lacking. We used a dual antagonist of Toll-like receptor (TLR) 7 and TLR9 to selectively inhibit responses of pDC but not other mononuclear phagocytes to viral RNA prior to and for 8 weeks following pathogenic simian immunodeficiency virus (SIV) infection of rhesus macaques. We show that pDC are major but not exclusive producers of IFN-α that rapidly become unresponsive to virus stimulation following SIV infection, whereas myeloid DC gain the capacity to produce IFN-α, albeit at low levels. pDC mediate a marked but transient IFN-α response in lymph nodes during the acute phase that is blocked by administration of TLR7 and TLR9 antagonist without impacting pDC recruitment. TLR7 and TLR9 blockade did not impact virus load or the acute IFN-α response in plasma and had minimal effect on expression of IFN-stimulated genes in both blood and lymph node. TLR7 and TLR9 blockade did not prevent activation of memory CD4+ and CD8+ T cells in blood or lymph node but led to significant increases in proliferation of both subsets in blood following SIV infection. Our findings reveal that virus-mediated activation of pDC through TLR7 and TLR9 contributes to substantial but transient IFN-α production following pathogenic SIV infection. However, the data indicate that pDC activation and IFN-α production are unlikely to be major factors in driving immune activation in early infection. Based on these findings therapeutic strategies aimed at blocking pDC function and IFN-α production may not reduce HIV-associated immunopathology. © 2013 Kader et al

Precision Measurement of the Mass of the h_c(1P1) State of Charmonium

A precision measurement of the mass of the h_c(1P1) state of charmonium has been made using a sample of 24.5 million psi(2S) events produced in e+e- annihilation at CESR. The reaction used was psi(2S) -> pi0 h_c, pi0 -> gamma gamma, h_c -> gamma eta_c, and the reaction products were detected in the CLEO-c detector. Data have been analyzed both for the inclusive reaction and for the exclusive reactions in which eta_c decays are reconstructed in fifteen hadronic decay channels. Consistent results are obtained in the two analyses. The averaged results of the present measurements are M(h_c)=3525.28+-0.19 (stat)+-0.12(syst) MeV, and B(psi(2S) -> pi0 h_c)xB(h_c -> gamma eta_c)= (4.19+-0.32+-0.45)x10^-4. Using the 3PJ centroid mass, Delta M_hf(1P)= - M(h_c) = +0.02+-0.19+-0.13 MeV.Comment: 9 pages, available through http://www.lns.cornell.edu/public/CLNS/, submitted to PR

Precision Measurement of B(D+ -> mu+ nu) and the Pseudoscalar Decay Constant fD+

We measure the branching ratio of the purely leptonic decay of the D+ meson with unprecedented precision as B(D+ -> mu+ nu) = (3.82 +/- 0.32 +/- 0.09)x10^(-4), using 818/pb of data taken on the psi(3770) resonance with the CLEO-c detector at the CESR collider. We use this determination to derive a value for the pseudoscalar decay constant fD+, combining with measurements of the D+ lifetime and assuming |Vcd| = |Vus|. We find fD+ = (205.8 +/- 8.5 +/- 2.5) MeV. The decay rate asymmetry [B(D+ -> mu+ nu)-B(D- -> mu- nu)]/[B(D+ -> mu+ nu)+B(D- -> mu- nu)] = 0.08 +/- 0.08, consistent with no CP violation. We also set 90% confidence level upper limits on B(D+ -> tau+ nu) < 1.2x10^(-3) and B(D+ -> e+ nu) < 8.8x10^(-6).Comment: 24 pages, 11 figures and 6 tables, v2 replaced some figure vertical axis scales, v3 corrections from PRD revie