Abrogation of neuraminidase reduces biofilm formation, capsule biosynthesis, and virulence of Porphyromonas gingivalis.

The oral bacterium Porphyromonas gingivalis is a key etiological agent of human periodontitis, a prevalent chronic disease that affects up to 80% of the adult population worldwide. P. gingivalis exhibits neuraminidase activity. However, the enzyme responsible for this activity, its biochemical features, and its role in the physiology and virulence of P. gingivalis remain elusive. In this report, we found that P. gingivalis encodes a neuraminidase, PG0352 (SiaPg). Transcriptional analysis showed that PG0352 is monocistronic and is regulated by a sigma70-like promoter. Biochemical analyses demonstrated that SiaPg is an exo-α-neuraminidase that cleaves glycosidic-linked sialic acids. Cryoelectron microscopy and tomography analyses revealed that the PG0352 deletion mutant (ΔPG352) failed to produce an intact capsule layer. Compared to the wild type, in vitro studies showed that ΔPG352 formed less biofilm and was less resistant to killing by the host complement. In vivo studies showed that while the wild type caused a spreading type of infection that affected multiple organs and all infected mice were killed, ΔPG352 only caused localized infection and all animals survived. Taken together, these results demonstrate that SiaPg is an important virulence factor that contributes to the biofilm formation, capsule biosynthesis, and pathogenicity of P. gingivalis, and it can potentially serve as a new target for developing therapeutic agents against P. gingivalis infection.

Association of interleukin 10 and interferon gamma gene polymorphisms with enterovirus 71 encephalitis in patients with hand, foot and mouth disease.

Enterovirus 71 (EV71) is one of the common causative agents of hand, foot and mouth disease (HFMD), and is associated with several outbreaks with neurological complications including encephalitis. This study investigated the polymorphisms of interferon gamma (IFN-γ)+874 T/A and interleukin 10 (IL-10)-1082 G/A in 65 Chinese patients with EV71 encephalitis and 113 Chinese HFMD patients without complications. The polymorphisms of IFN-γ+874 T/A and IL-10-1082 G/A were determined by polymerase chain reaction (PCR)-amplification refractory mutation system (ARMS) and PCR-sequence-specific primer (SSP) analysis, respectively. The IFN-γ + 874 A allele was observed with significantly greater frequency in patients with EV71 encephalitis (76.2%) compared with HFMD patients without complications (61.1%, p < 0.01). Similarly, the IL-10 - 1082 A allele was observed with significantly greater frequency in patients with EV71 encephalitis (86.2%) compared with HFMD patients without complications (77.0%, p < 0.05). IFN-γ + 874 A and IL-10 - 1082 A alleles are associated with susceptibility to EV71 encephalitis in Chinese patients.

De novo acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2): a clinicopathologic and cytogenetic study of an entity recently added to the WHO classification.

Acute myeloid leukemia with inv(3)(q21q26.2) or t(3;3)(q21;q26.2) is a rare type of leukemia recently added to the World Health Organization (WHO) classification scheme. In this study, we analyzed the clinicopathologic and cytogenetic features of 30 cases of de novo acute myeloid leukemia with inv(3)/t(3;3). The median patient age was 53 years (range, 27-77 years). The platelet count was variable (range, 21-597 × 10(9)/l, median: 128 × 10(9)/l), and two (6.7%) patients presented with thrombocytosis (>450 × 10(9)/l). Morphologically, these neoplasms showed a spectrum of findings. Myelomonocytic differentiation was most common in 11 (37%) cases. Morphological evidence of dysplasia was observed in at least one lineage in 23 of 25 (92%) cases in which maturing elements could be assessed. In all, 5 (17%) patients had isolated inv(3) or t(3;3) and 25 (83%) patients had additional cytogenetic abnormalities, most often monosomy 7 (40%). Eleven (37%) patients had a complex karyotype (≥ 3 additional abnormalities). FLT3 gene mutation by internal tandem duplication was identified in 2 of 23 (9%) cases assessed. No clinical, pathological, or cytogenetic features independent of inv(3) or t(3;3) correlated with a worse outcome. However, patients treated with allogeneic stem cell transplantation (n=11) had a significantly better survival than did those treated with chemotherapy alone (n=17) (13.8 vs 8.0 months, P=0.041). We conclude that de novo acute myeloid leukemia associated with inv(3)/t(3;3) is an aggressive type of leukemia regardless of morphological or karyotypic findings, supporting the inclusion of this disease as a specific entity defined by inv(3)/t(3;3) in the WHO classification. Allogeneic stem cell transplantation seems to improve outcome in patients with this disease.

Numerous cortical tubers and rhabdomyomas in a case of sudden unexpected infant death.

Sudden infant death syndrome is the leading cause of death in infants between the ages of 1 month to 1 year. Sudden infant death syndrome, a diagnosis of exclusion, can only be made after other explanations for unexpected death have been ruled out. Tuberous sclerosis complex is occasionally the findings in these patients with unexpected infant death. Here, we present a case of an unexpected infant death during sleep with multiple factors that confound the cause of death. We discuss these factors and attempt to delineate their contributions to arrive at a cause and mechanism of death.

The Central Response of Electroacupuncture on Trigeminal Neuralgia Based on Resting-State Functional Magnetic Resonance Imaging: A Protocol for a Pre-Experimental, Single-Centre, Randomized, Controlled Trial.

OBJECTIVE: To verify the efficacy of electroacupuncture (EA) on classical trigeminal neuralgia (CTN), and to observe the brain functional status of patients with CTN and the intervention effects of EA on brain function by resting-state functional magnetic resonance imaging (rs-fMRI). METHODS AND ANALYSIS: Thirty CTN patients will be randomly divided into EA combined with carbamazepine group and carbamazepine group in 2:1 ratio by using a random number table. Patients in EA combined with carbamazepine will receive EA treatment and carbamazepine for four weeks. The carbamazepine group will only receive carbamazepine treatment. VAS (visual analogue scale), HAMA (Hamilton Anxiety Scale), HAMD (Hamilton Depression Scale) and SF-36 (short form 36 health survey) will be performed before, after four-week treatments and at three-month follow-up in CTN patients. Six CTN patients will be randomly selected from EA combined with carbamazepine group and carbamazepine group, respectively, before treatment, and twelve paired healthy participants will be recruited at the same time. The twelve CTN patients will be scanned by rs-fMRI before and after treatment, and the healthy participants will be scanned by rs-fMRI only at baseline. Regional homogeneity (ReHo) and amplitude of low-frequency fluctuation (ALFF) analysis will be carried out to compare the dysfunctional brain regions between CTN patients and healthy participants, as well as the differences between two groups of patients with CTN after treatment. TRIAL REGISTRATION: ChiCTR-1900027873.

Trisomy 14 as a sole chromosome abnormality is associated with older age, a heterogenous group of myeloid neoplasms with dysplasia, and a wide spectrum of disease progression.

Trisomy 14 is a rare recurrent cytogenetic abnormality in myeloid neoplasms; however, its clinicopathologic features have not been well described. We report the clinicopathologic, immunophenotypic, and molecular genetic features of 16 cases of myeloid neoplasms with isolated trisomy 14. Our results show that cases with isolated trisomy 14 encompass a heterogeneous group of myeloid neoplasms including myelodysplastic syndrome (MDS, 44%), myelodysplastic/myeloproliferative neoplasms (31%), and acute myeloid leukemia (25%). The patients are usually elder (median age 71 years), and there is a male predominance (82%). Multilineage dysplasia is noted in all cases. Oncogenic mutations of genes involved in cell proliferation and/or survival rarely occur. Compared with cases of MDS with diploid karyotype, patients of MDS with isolated trisomy 14 demonstrate a similar overall survival and rate of leukemia transformation.

Multiple pathologies in the kidney biopsy of a recently pregnant woman.

We report a 42-year-old woman with underlying hypertension, mild renal dysfunction and proteinuria who presented as an obstetric emergency with uncontrolled hypertension and nephrotic syndrome. The rapid deterioration in her kidney function and worsening of her symptoms led to an urgent termination of her twin pregnancy. Although a clinical improvement was noticed within 10 days, the persistently elevated serum creatinine required further evaluation. A kidney biopsy showed changes consistent with acute tubular necrosis and resolving preeclampsia superimposed on focal segmental glomerulosclerosis and hypertensive kidney disease. The importance of a kidney biopsy in confirming clinical suspicions and determining patient prognosis is emphasized.

Myelodysplastic syndrome with inv(3)(q21q26.2) or t(3;3)(q21;q26.2) has a high risk for progression to acute myeloid leukemia.

Acute myeloid leukemia (AML) with inv(3) (q21q26.2) or t(3;3)(q21;q26.2) is a distinct subtype in the World Health Organization classification. The natural history of myelodysplastic syndrome (MDS) associated with these cytogenetic aberrations is poorly understood. We studied 17 MDS (11 de novo and 6 therapy related) and 3 chronic myelomonocytic leukemia (CMML) cases associated with inv(3) (q21q26.2) or t(3;3)(q21;q26.2). The de novo cases were further classified as refractory cytopenia with multilineage dysplasia (n = 8) and refractory anemia with excess blasts (n = 3). Isolated inv(3)/t(3;3) was identified in 4 cases, whereas -7/7q (n = 13) and -5/5q (n = 6) were common additional aberrations. Nineteen patients died, including 13 in whom the disease progressed to AML after a median of 7 months. Median survival for patients with de novo disease was similar to that for patients with therapy-related MDS (13 vs 17.5 months). MDS or CMML with inv(3)/t(3;3) are aggressive diseases with a high risk of progression to AML.

Chromosome 20q deletion: a recurrent cytogenetic abnormality in patients with chronic myelogenous leukemia in remission.

del(20q) can be observed in hematologic neoplasms, including chronic myelogenous leukemia (CML), and has been reported in patients undergoing blast transformation. We describe 10 patients with CML in hematologic and cytogenetic remission with del(20q) detected by conventional cytogenetics. There were 6 men and 4 women with a median age of 56 years. All patients initially had BCR-ABL1 and t(9;22) (q34;q11.2) and achieved morphologic and cytogenetic remission after therapy. del(20q) was identified before (2/10 [20%]), at the time of (3/10 [30%]), or after (5/10 [50%]) cytogenetic remission and was not associated with morphologic evidence of dysplasia. At last follow-up, no patients had a myelodysplastic syndrome (MDS). Leukocyte and platelet counts were normal; 4 of 10 patients had mild anemia. Nine patients have remained in morphologic and cytogenetic remission with stable del(20q). BCR-ABL1 fusion transcript levels were absent or low (median, 0.01%). Recently, in 1 patient, recurrent CML developed and del(20q) was lost. We conclude that del(20q) in the setting of CML in remission is not predictive of MDS or blast transformation.

Plasmablastic lymphoma involving the penis: a previously unreported location of a case with aberrant CD3 expression.

Lymphomas of the penis are rare and can either arise at this site or be a manifestation of systemic disease. We report the case of an elderly man with a plasmablastic lymphoma (PBL) involving the uncircumcised penile prepuce. The neoplasm was composed of plasmablasts positive for monotypic immunoglobulin lambda light chain, CD3, CD79a, CD138 and Epstein-Barr virus encoded RNA (EBER), and was negative for CD2, CD5, CD7, CD20, and PAX5. This case is highly unusual for at least two reasons. The penile foreskin is a rare location for lymphoma and PBL at this site has not been reported. Secondly, the tumour was shown by immunohistochemistry to be positive for the T-cell marker CD3. Lineage ambiguity in terminally differentiated B-cell lymphomas has been reported to be closely related with immune compromise and is associated with Epstein-Barr virus infection. The literature on penile lymphomas is also reviewed.

Stimulation-dependent recycling of integrin beta1 regulated by ARF6 and Rab11.

In comparison to the internalization pathways of endocytosis, the recycling pathways are less understood. Even less defined is the process of regulated recycling, as few examples exist and their underlying mechanisms remain to be clarified. In this study, we examine the endocytic recycling of integrin beta1, a process that has been suggested to play an important role during cell motility by mediating the redistribution of integrins to the migrating front. External stimulation regulates the endocytic itinerary of beta1, mainly at an internal compartment that is likely to be a subset of the recycling endosomes. This stimulation-dependent recycling is regulated by ARF6 and Rab11, and also requires the actin cytoskeleton in an ARF6-dependent manner. Consistent with these observations being relevant for cell motility, mutant forms of ARF6 that affect either actin rearrangement or recycling inhibit the motility of a breast cancer cell line.