Background: Antipsychotics are commonly used to treat delirium but can adversely affect the extrapyramidal and cardiac conduction systems. Antipsychotic use has also been reported to be associated ...with increased mortality in older adults. Therefore, alternative and adjunct medications for delirium are necessary. We retrospectively assessed the efficacy and safety of gabapentin (GBP) as an alternative and adjunct medication for delirium. Methods: We retrospectively investigated the records of patients with delirium treated with GBP (71 patients; median age, 81 years; interquartile range, 76-87.5 years; 54.9% males) at a general hospital. We examined duration to delirium improvement, as assessed by the Intensive Care Delirium Screening Checklist (ICDSC) and DSM-5 criteria, as well as adverse events. Results: The median (interquartile range) GBP dose was 200 mg (150-350 mg) /day. A total of 71.8% and 85.9% of the patients failed to meet the diagnostic criteria for delirium at 2 days and 5 days after initial administration, respectively (p<0.05). In subgroup analysis, patients with a history of epilepsy or cerebrovascular disease responded better to GBP than did those without such histories, suggesting that patients with abnormal/borderline neuronal activity respond to GBP even though they do not exhibit seizures. GBP did not induce extrapyramidal symptoms, cardiac conduction disturbances, hyperglycemia, or epilepsy but caused sleepiness and myoclonus. Conclusions: GBP may improve delirium with fewer adverse effects and may be a safe alternative or adjunct treatment for delirium. Dosage adjustment may be necessary to prevent sleepiness.
Autotaxin (ATX) is a cancer-associated motogen that has multiple biological activities in vitro through the production of bioactive small lipids, lysophosphatidic acid (LPA). ATX and LPA are ...abundantly present in circulating blood. However, their roles in circulation remain to be solved. To uncover the physiological role of ATX we analyzed ATX knock-out mice. In ATX-null embryos, early blood vessels appeared to form properly, but they failed to develop into mature vessels. As a result ATX-null mice are lethal around embryonic day 10.5. The phenotype is much more severe than those of LPA receptor knock-out mice reported so far. In cultured allantois explants, neither ATX nor LPA was angiogenic. However, both of them helped to maintain preformed vessels by preventing disassembly of the vessels that was not antagonized by Ki16425, an LPA receptor antagonist. In serum from heterozygous mice both lysophospholipase D activity and LPA level were about half of those from wild-type mice, showing that ATX is responsible for the bulk of LPA production in serum. The present study revealed a previously unassigned role of ATX in stabilizing vessels through novel LPA signaling pathways.
Let
p
be a prime number with
p
≡
5
(
mod
8
)
. We construct a new infinite family of pairs of imaginary cyclic fields of degree
(
p
-
1
)
/
2
with both class numbers divisible by
p
. Let
k
0
be the ...unique subfield of
Q
(
ζ
p
)
of degree
(
p
-
1
)
/
4
and
u
p
=
(
t
+
b
p
)
/
2
(
>
1
)
be the fundamental unit of
k
:
=
Q
(
p
)
. We put
D
m
,
n
:
=
L
m
(
2
F
m
-
F
n
L
m
)
b
for integers
m
and
n
, where
{
F
n
}
and
{
L
n
}
are linear recurrence sequences of degree two associated to the characteristic polynomial
P
(
X
)
=
X
2
-
t
X
-
1
. We assume that there exists a pair
(
m
0
,
n
0
)
of integers satisfying certain congruence relations. Then we show that there exists a positive integer
N
q
which satisfies the both class numbers of
k
0
(
D
m
,
n
)
and
k
0
(
p
D
m
,
n
)
are divisible by
p
for any pairs (
m
,
n
) with
m
≡
m
0
(
mod
N
q
)
,
n
≡
n
0
(
mod
N
q
)
and
n
>
3
. Furthermore, we show that if we assume that ERH holds, then there exists the pair
(
m
0
,
n
0
)
.
Th17 cells are key players in defense against pathogens and maintaining tissue homeostasis, but also act as critical drivers of autoimmune diseases. Based on single-cell RNA-seq profiling of ...pathogenic versus nonpathogenic Th17 cells, we identified protein C receptor (PROCR) as a cell surface molecule expressed in covariance with the regulatory module of Th17 cells. Although PROCR expression in T cells was controlled by the cooperative action of the Th17 lineage-specific transcription factors RORγt, IRF4, and STAT3, PROCR negatively regulated Th17 differentiation. CD4
T cells from PROCR low expressor mutant mice readily differentiated into Th17 cells, whereas addition of the PROCR ligand, activated protein C, inhibited Th17 differentiation in vitro. In addition, PROCR acted as a negative regulator of Th17 pathogenicity in that it down-regulated expression of several pathogenic signature genes, including IL-1 and IL-23 receptors. Furthermore, T cell-specific deficiency of PROCR resulted in the exacerbation of experimental autoimmune encephalomyelitis (EAE) and higher frequencies of Th17 cell in vivo, indicating that PROCR also inhibits pathogenicity of Th17 cells in vivo. PROCR thus does not globally inhibit Th17 responses but could be targeted to selectively inhibit proinflammatory Th17 cells.
Ramelteon for Delirium in Hospitalized Patients Hatta, Kotaro; Kishi, Yasuhiro; Wada, Ken
JAMA : the journal of the American Medical Association,
09/2015, Letnik:
314, Številka:
10
Journal Article
The Japanese Psycho-Oncology Society and Japanese Association of Supportive Care in Cancer recently launched the clinical practice guidelines for delirium in adult cancer patients. The aim of the ...guidelines was to provide evidence-based recommendations for the clinical assessment and management of delirium in cancer patients. This article reports the process of developing the guideline and summarizes the recommendations made.
The guidelines were developed in accordance with the Medical Information Network Distribution Service creation procedures. The guideline development group, consisting of multidisciplinary members, formulated nine clinical questions. A systematic literature search was conducted to identify relevant articles published prior to through 31 May 2016. Each article was reviewed by two independent reviewers. The level of evidence and the strength of the recommendations were graded using the grading system developed by the Medical Information Network Distribution Service, following the concept of The Grading of Recommendations Assessment, Development and Evaluation system. The modified Delphi method was used to validate the recommendation statements.
This article provides a summary of the recommendations with rationales for each, as well as a short summary.
These guidelines will support the clinical assessment and management of delirium in cancer patients. However, additional clinical studies are warranted to further improve the management of delirium.
Abstract Objective Delirium in the intensive care unit (ICU) is recognized as a major public health problem. Few Japanese outcome studies have been reported. The purpose of the study was to ...investigate the hospital outcomes of ICU delirium in a Japanese general hospital. Methods Patients were drawn from consecutive admissions to an ICU at a tertiary care university hospital. Delirium assessments were conducted using the Intensive Care Delirium Screening Checklist (ICDSC). The following information was recorded: age, sex, the reason for ICU admission, the ICDSC scores, the COmplexity PRediction Instrument (COMPRI) scores, the length of stay (LOS) in the ICU, the total hospital LOS, hospital outcomes and social worker’s consultation. Results Of the 126 patients who were evaluated, 35 (27.8%) developed delirium during the ICU stay. Older age and biopsychosocial vulnerability assessed by the COMPRI were risk factors of ICU delirium. ICU delirium was a predictor of increased mortality and associated with prolonged ICU and hospital LOS. ICU delirium was an independent risk factor for having social worker’s consultation after ICU discharge. Conclusions ICU delirium is associated with worse outcomes including mortality and LOS in Japan. ICU delirium is independently associated with further social worker’s consultations, suggesting that early proactive social worker’s intervention may be beneficial for the patients with ICU delirium.
Autotaxin (ATX) is a multifunctional phosphodiesterase originally isolated from melanoma cells as a potent cell motility-stimulating factor. ATX is identical to lysophospholipase D, which produces a ...bioactive phospholipid, lysophosphatidic acid (LPA), from lysophosphatidylcholine (LPC). Although enhanced expression of ATX in various tumor tissues has been repeatedly demonstrated, and thus, ATX is implicated in progression of tumor, the precise role of ATX expressed by tumor cells was unclear. In this study, we found that ATX is highly expressed in glioblastoma multiforme (GBM), the most malignant glioma due to its high infiltration into the normal brain parenchyma, but not in tissues from other brain tumors. In addition, LPA1, an LPA receptor responsible for LPA-driven cell motility, is predominantly expressed in GBM. One of the glioblastomas that showed the highest ATX expression (SNB-78), as well as ATX-stable transfectants, showed LPA1-dependent cell migration in response to LPA in both Boyden chamber and wound healing assays. Interestingly these ATX-expressing cells also showed chemotactic response to LPC. In addition, knockdown of the ATX level using small interfering RNA technique in SNB-78 cells suppressed their migratory response to LPC. These results suggest that the autocrine production of LPA by cancer cell-derived ATX and exogenously supplied LPC contribute to the invasiveness of cancer cells and that LPA1, ATX, and LPC-producing enzymes are potential targets for cancer therapy, including GBM.
In this paper, we prove that the 3-rank of the ideal class group of the imaginary quadratic field Q(4−318n+3) is at least 3 for every positive integer n.
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