Serine/Threonine Kinase 11 Plays a Canonical Role in Malignant Progression of KRAS -Mutant and GNAS -Wild-Type Intraductal Papillary Mucinous Neoplasms of the Pancreas.

OBJECTIVE: We aimed to elucidate the clinicopathobiological significance of Serine/Threonine Kinase 11 (STK11) in pancreatic intraductal papillary mucinous neoplasms (IPMNs). BACKGROUND: STK11 is a tumor suppressor involved in certain IPMNs; however, its significance is not well known. METHODS: In 184 IPMNs without Peutz-Jeghers syndrome, we analyzed expression of STK11 and phosphorylated-AMPKa in all cases, and p16, p53, SMAD4, and ß-catenin in 140 cases by immunohistochemistry; and we analyzed mutations in 37 genes, including whole coding exons of STK11, CDKN2A, TP53, and SMAD4, and hotspots of KRAS, BRAF, and GNAS in 64 cases by targeted sequencing. KRAS and GNAS were additionally analyzed in 86 STK11-normal IPMNs using digital-PCR. RESULTS: Consistent loss or reduction of STK11 expression was observed in 26 of 184 (14%) IPMNs. These STK11-aberrant IPMNs were 17 of 45 (38%) pancreatobiliary, 8 of 27 (30%) oncocytic, 1 of 54 (2%) gastric, and 0 of 58 (0%) intestinal subtypes ( P = 8.5E-11), and 20 of 66 (30%) invasive, 6 of 74 (8%) high-grade, and 0 of 44 (0%) low-grade ( P = 3.9E-06). Sixteen somatic STK11 mutations (5 frameshift, 6 nonsense, 1 splicing, and 4 missense) were detected in 15/26 STK11-aberrant IPMNs ( P = 4.1E-06). All STK11-aberrantIPMNs were GNAS -wild-type and 96% of them were KRAS or BRAF -mutant.Morphologically, STK11-aberrant IPMNs presented "fern-like" arborizing papillae with thin fibrovascular core. Phosphorylated-AMPKa was down-regulated in STK11-aberrant IPMNs (92%, P = 6.8E-11). Patients with STK11-aberrant IPMNs showed poorer survival than patients with STK11-normal IPMNs ( P = 3.6E-04 overall; P = 6.1E-04 disease-free). CONCLUSION: STK11 may play a canonical role in malignant progression and poor survival of patients with IPMNs. Aberrant STK11-driven phosphorylated AMPK downregulation may provide therapeutic opportunities with mTOR inhibitors/AMPK activators.

Feelings of older Japanese primiparous couples and satisfaction of older primiparous wives with their husbands' support during pregnancy: Focus on the perceptions of pregnant couples.

Aim: This study was to explore the feelings of older primiparous wives and husbands and satisfaction of older primiparous wives with their husbands' support during pregnancy. Design: This study is a qualitative research design based on the characteristics of clarifying the recognition of older primiparous couples. Methods: Participants were eight older Japanese primiparous couples. Older primiparous couple's feeling and support by husband during pregnancy were elected using semi-structured interviews. The analysis was used by content analysis method. Results: Two categories of the couples' feeling during pregnancy included "Mental stress and physical burden associated with older age" and "Richness and strong will to actively accept the older age." Three categories of the husbands' support for wives' satisfaction included "Empathy regarding the older primiparous wives," "physical and mental health" and "Cooperation of housework with husband." This study has greatly contributed to nursing support for marital relationships.

Comparative study of ipsilesional and contralesional repetitive transcranial magnetic stimulations for acute infarction.

BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) is reported to improve chronic post-stoke hemiparesis. However, application of rTMS during the acute phase of post-stroke has not fully been investigated. We investigated the safety and the efficacy of intermittent theta-burst stimulation (iTBS) of the affected motor cortex and 1-Hz stimulation of the unaffected hemisphere during the acute phase in patients with hemiparesis due to capsular infarction. METHODS: Twenty one patients who met the study criteria were randomly assigned to receive, starting within 7days after stroke onset and for a period of 10days, iTBS of the affected motor cortex hand area (n=8), 1-Hz stimulation of the unaffected motor cortex hand area (n=7), or sham stimulation (n=6). Upper limb motor function was evaluated before rTMS and 12weeks after onset of the stroke. Evaluation was based on the Fugl-Meyer Assessment (FMA), Stroke Impairment Assessment Set (SIAS), Modified Ashworth Scale (MAS), grip strength, and motor evoked potential (MEP) amplitude in the first dorsal interosseous (FDI) muscle. RESULTS: Both iTBS applied to the affected motor cortex hand area and 1-Hz stimulation applied to the unaffected motor cortex hand area enhanced motor recovery. In comparison to sham stimulation, iTBS increased the SIAS finger-function test score, and 1-Hz stimulation decreased the MAS wrist and finger score. CONCLUSIONS: Ipsilesional iTBS and contralesional 1-Hz stimulation applied during the acute phase of stroke have different effects: ipsilesional iTBS improves movement of the affected limb, whereas contralesional 1-Hz stimulation reduces spasticity of the affected limb.

[A case with apraxia of tool use: selective inability to form a hand posture for a tool].

Impaired tool use is recognized as a symptom of ideational apraxia. While many studies have focused on difficulties in producing gestures as a whole, using tools involves several steps; these include forming hand postures appropriate for the use of certain tool, selecting objects or body parts to act on, and producing gestures. In previously reported cases, both producing and recognizing hand postures were impaired. Here we report the first case showing a selective impairment of forming hand postures appropriate for tools with preserved recognition of the required hand postures. A 24-year-old, right-handed man was admitted to hospital because of sensory impairment of the right side of the body, mild aphasia, and impaired tool use due to left parietal subcortical hemorrhage. His ability to make symbolic gestures, copy finger postures, and orient his hand to pass a slit was well preserved. Semantic knowledge for tools and hand postures was also intact. He could flawlessly select the correct hand postures in recognition tasks. He only demonstrated difficulties in forming a hand posture appropriate for a tool. Once he properly grasped a tool by trial and error, he could use it without hesitation. These observations suggest that each step of tool use should be thoroughly examined in patients with ideational apraxia.

Bone marrow-derived microglia infiltrate into the paraventricular nucleus of chronic psychological stress-loaded mice.

BACKGROUND: Microglia of the central nervous system act as sentinels and rapidly react to infection or inflammation. The pathophysiological role of bone marrow-derived microglia is of particular interest because they affect neurodegenerative disorders and neuropathic pain. The hypothesis of the current study is that chronic psychological stress (chronic PS) induces the infiltration of bone marrow-derived microglia into hypothalamus by means of chemokine axes in brain and bone marrow. METHODS AND FINDINGS: Here we show that bone marrow-derived microglia specifically infiltrate the paraventricular nucleus (PVN) of mice that received chronic PS. Bone marrow derived-microglia are CX3CR1(low)CCR2(+)CXCR4(high), as distinct from CX3CR1(high)CCR2(-)CXCR4(low) resident microglia, and express higher levels of interleukin-1ß (IL-1ß) but lower levels of tumor necrosis factor-α (TNF-α). Chronic PS stimulates the expression of monocyte chemotactic protein-1 (MCP-1) in PVN neurons, reduces stromal cell-derived factor-1 (SDF-1) in the bone marrow and increases the frequency of CXCR4(+) monocytes in peripheral circulation. And then a chemokine (C-C motif) receptor 2 (CCR2) or a ß3-adrenoceptor blockade prevents infiltration of bone marrow-derived microglia in the PVN. CONCLUSION: Chronic PS induces the infiltration of bone marrow-derived microglia into PVN, and it is conceivable that the MCP-1/CCR2 axis in PVN and the SDF-1/CXCR4 axis in bone marrow are involved in this mechanism.

Transient heating of expressed breast milk up to 65°C inactivates HIV-1 in milk: a simple, rapid, and cost-effective method to prevent postnatal transmission.

The postnatal transmission of human immunodeficiency virus (HIV) from mothers to children occurs through breastfeeding. Although heat treatment of expressed breast milk is a promising approach to make breastfeeding safer, it is still not popular, mainly because the recommended procedures are difficult to follow, or time-consuming, or because mothers do not know which temperature is sufficient to inactivate HIV without destroying the nutritional elements of milk. To overcome these drawbacks, a simple and rapid method of heat treatment that a mother could perform with regular household materials applying her day-to-day art of cooking was examined. This structured experiment has demonstrated that both cell-free and cell-associated HIV type 1 (HIV-1) in expressed breast milk could be inactivated once the temperature of milk reached 65°C. Furthermore, a heating method as simple as heating the milk in a pan over a stove to 65°C inhibited HIV-1 transmission retaining milk's nutritional key elements, for example, total protein, IgG, IgA, and vitamin B(12) . This study has highlighted a simple, handy, and cost-effective method of heat treatment of expressed breast milk that mothers infected with HIV could apply easily and with more confidence.

Seroprevalence of rubella and measles antibodies in Lao PDR.

BACKGROUND: Nowadays, measles and rubella epidemics still occur worldwide, particularly in developing countries. METHODS: The present study investigated seroprevalence of rubella and measles IgG antibodies by using a comercial enzyme immunoassay. The findings helped to understand the current status of these infections in school children in Vientiane Capital, Lao PDR. RESULTS: The seropositive rate for measles antibody was 97.6%. Most importantly, more than half of 411 healthy children (56.4%) were rubella seronegative and susceptible to acquired rubella infection. CONCLUSIONS: The results highlight a high proportion of rubella-seronegative children, suggesting that they are susceptible to rubella and face the risk of congenital rubella syndrome. It was the first study to report on seroprevalence of rubella in Vientiane Capital, Lao PDR.

Quantitative and qualitative assay of rubella IgA antibody in breast milk.

Breast milk contains immunological factors, such as IgA antibody, which help to prevent infectious diseases. A total of 197 paired samples of colostrum and breast milk was collected from postpartum mothers in Gunma City, Japan, and examined for anti-rubella IgA antibody by enzyme-linked immunosorbent assay (ELISA) and Western blotting (WB). The anti-rubella virus IgA ranged from 0.5 to 78.5 U/ml with a mean of 6.05 U/ml and a median of 3.6 U/ml in colostrum, and from 0.5 to 32.7 U/ml with a mean of 2.74 U/ml and a median of 2 U/ml in milk. The differences between the means of titers of total IgA and anti-rubella virus IgA in colostrum and in milk were significant statistically. The levels of anti-rubella virus IgA in both colostrum and breast milk correlated positively with the anti-rubella virus hemagglutination inhibition (HI) titers in the sera of mother, indicating that the levels of these different classes of antibodies correlated. Based on WB, anti-rubella virus IgA in both colostrum and breast milk reacted with the rubella viral protein E1 and C, but not with the E2 protein.

Molecular epidemiology of adenovirus infection among infants and children with acute gastroenteritis in Dhaka City, Bangladesh.

A total of 917 fecal specimens collected from infants and children with acute gastroenteritis in Dhaka City, Bangladesh during 2004-2005 were examined for the presence of adenoviruses by PCR. Adenoviruses were identified in 17 of 917 (1.9%) specimens. Detected adenoviruses were subjected to molecular genetic analysis by sequencing method. Adenoviruses detected in this study were classified into three serotypes, namely Ad9, Ad10 and Ad40. Of these, Ad40 was predominant, followed by Ad9 and accounted for 42% (7 of 17) and 36% (6 of 17), respectively. This is the first report of acute gastroenteritis attributed to Ad9 and Ad10 in Dhaka City, Bangladesh. Another interesting feature of the study was absence of Ad41 serotype. Our results clearly indicated that adenovirus infections were most commonly observed in winter season (October 2004 through January 2005) and in rainy season (May 2005 through July 2005) in Dhaka City. The most common clinical symptoms of adenovirus-infected patients were dehydration (94%), abdominal pain (59%) and vomiting (30%). To our knowledge, this is the first 1-year molecular epidemiological research of adenovirus infection in Bangladesh.

G2 strain of rotavirus among infants and children, Bangladesh.

To determine G and P genotypes, we performed nested PCR on 307 rotavirus specimens collected in Dhaka, Bangladesh, during 2004-2005. G2 (43.3%) was detected at the highest frequency, followed by G4 (19.5%), G9 (13.7%), G1 (12.7%), and G3 (2.6%). P[8] was the most predominant genotype (53.2%), followed by P[4] (42.9%).

First detection of IgA against norovirus in breast milk.

Breast milk samples (n = 239) collected from 1994-1997 from mothers at Chiba City, Japan, were tested for antinorovirus antibody by ELISA and western blot methods. It was found that 31 breast milk samples contained IgA against norovirus and this represented 13%. Breast milk could react with a diversity of norovirus genotypes. The highest number of samples containing IgA against norovirus was found in genotype GII/6 (11.3%) and the lowest in GI/8, GII/8 and GII/12 (each of 0.8%). Of note, twenty-eight samples showed reactivity to more than one different norovirus genotypes. Interestingly, three samples demonstrated cross-reaction with both norovirus genogroups I and II. This report is noteworthy because it is the first, to the best of our knowledge, demonstrating the presence of antibody against norovirus in breast milk.