High-responsivity graphene photodetectors integrated on silicon microring resonators.

Graphene integrated photonics provides several advantages over conventional Si photonics. Single layer graphene (SLG) enables fast, broadband, and energy-efficient electro-optic modulators, optical switches and photodetectors (GPDs), and is compatible with any optical waveguide. The last major barrier to SLG-based optical receivers lies in the current GPDs' low responsivity when compared to conventional PDs. Here we overcome this by integrating a photo-thermoelectric GPD with a Si microring resonator. Under critical coupling, we achieve >90% light absorption in a ~6 µm SLG channel along a Si waveguide. Cavity-enhanced light-matter interactions cause carriers in SLG to reach ~400 K for an input power ~0.6 mW, resulting in a voltage responsivity ~90 V/W, with a receiver sensitivity enabling our GPDs to operate at a 10-9 bit-error rate, on par with mature semiconductor technology, but with a natural generation of a voltage, rather than a current, thus removing the need for transimpedance amplification, with a reduction of energy-per-bit, cost, and foot-print.

Esophageal squamous cell carcinoma presenting with extensive skin lesions: a case report.

INTRODUCTION: Esophageal squamous cell carcinoma (ESCC) is the most common histological subtype of cancer in the upper and middle esophagus and is characterized by a high rate of mortality. The incidence of esophageal cancer varies greatly among regions of the world and occurs at a high frequency in Asia and South America. CASE PRESENTATION: In our department, a 51-year-old man was diagnosed with ESCC after presenting with extensive disseminated skin nodules. Biopsy of the nodules showed metastatic ESCC. Cutaneous manifestations of esophageal neoplasia are very rare and are mainly described for esophageal adenocarcinoma (EADC). Here we report a very uncommon case of extensive skin metastases of ESCC. CONCLUSION: Early biopsies of suspicious skin lesions are important and should be performed in patients with unclear symptoms such as weight loss or dysphagia and especially in patients with a history of cancer, since they can reveal the existence of a distant malignant disease leading to diagnosis and prompt therapy.

Diabetes mellitus associated with atypical antipsychotic medications: new case report and review of the literature.

BACKGROUND: Since the introduction of atypical antipsychotic medications, beginning with clozapine in 1990, several case reports in the psychiatric literature have suggested that they might be associated with new onset of diabetes mellitus as well as with diabetic ketoacidosis. METHODS: We report the case of a 38-year-old patient with schizophrenia who suddenly developed diabetes mellitus and ketoacidosis 12 months after starting olanzapine. Similar cases in the literature were found through a MEDLINE-assisted search using the key words "schizophrenia," "diabetes mellitus," "ketoacidosis," and "adverse drug reaction." RESULTS: Including this case, 30 patients have been reported in the literature to have developed diabetes or have lost diabetic control after starting clozapine, olanzapine, or quetiapine. Twelve of these 30 developed diabetic ketoacidosis. Two limited quantitative studies have added evidence toward this association. CONCLUSION: Although a causal relation has not been definitively proved, the number of cases reported in the literature suggests there might be an association between atypical antipsychotic medications and diabetes mellitus. Primary care physicians who care for patients with schizophrenia should be aware of this possible association.

Delay in treatment of biliary disease during pregnancy increases morbidity and can be avoided with safe laparoscopic cholecystectomy.

Recent reports indicate that laparoscopic cholecystectomy in pregnancy is safe. The aim of this study was to evaluate whether delays in definitive treatment of symptomatic cholelithiasis increase morbidity. We reviewed the records of 16 women who underwent laparoscopic cholecystectomy during pregnancy between 1992 and 1999. Mean age was 24 +/- 5 years (mean +/- standard error). Symptom onset was during the first trimester in nine patients, second trimester in six patients, and third trimester in one patient. Patients had abdominal pain (93%), nausea (93%), emesis (80%), and fever (66%) for a median of 45 days (range 1-195 days) before cholecystectomy. Nine of 11 women who underwent cholecystectomy more than 5 weeks after onset of symptoms experienced recurrent attacks necessitating 15 hospital admissions and four emergency room visits. Moreover four women who developed symptoms in the first and second trimesters but whose operations were delayed to the third trimester had 11 hospital admissions and four emergency room visits; three of those four (75%) women developed premature contractions necessitating tocolytics. Cholecystectomy was completed laparoscopically in 14 women. There was no hospital infant or maternal mortality or morbidity. We recommend prompt laparoscopic cholecystectomy in pregnant women with symptomatic biliary disease because it is safe and it reduces hospital admissions and frequency of premature labor.

Crossing diagnostic borders: herpes encephalitis complicated by cultural and language barriers.

BACKGROUND: The patient who complains of vague mental status changes requires extra vigilance in that the underlying condition might itself affect the patient's ability to communicate well and relate a medical history. The differential diagnosis of delirium is broad, ranging from the benign to the potentially fatal. The diagnostic uncertainty inherent in primary care is compounded when language and cultural differences interfere with physician-patient communication. METHODS: We undertook a MEDLINE-assisted review of the medical literature concerning herpes simplex encephalitis. Additionally, we performed an Internet search of several government Web sites to find current legal and federal guidelines concerning the use of medical interpreters. RESULTS AND CONCLUSIONS: We recount the case of a young Eastern European immigrant who complained initially of vague mental status changes and was found to have herpes simplex encephalitis. Diagnosis could have been made sooner had the physician been familiar with the patient's baseline mental status or had cultural and language barriers not stood between the physician and the patient and his mother. Herpes simplex encephalitis is a rare, but specific, cause of delirium for which prompt diagnosis and treatment with intravenous acyclovir can prevent death or serious sequelae.

Laparoscopic revision of failed antireflux operations.

BACKGROUND: A small number of patients fail fundoplication and require reoperation. Laparoscopic techniques have been applied to reoperative fundoplications. We reviewed our experience with reoperative laparoscopic fundoplication. METHODS: Reoperative laparoscopic fundoplication was undertaken in 28 patients, 19 F and 9 M, of mean age 56 years +/- 12. Previous antireflux procedures included 19 open and 12 laparoscopic antireflux operations. RESULTS: Symptoms were heartburn (90%), dysphagia (35%), and atypical symptoms (30%%). The mean interval from antireflux procedure to revision was 13 months +/- 4.2. The mean DeMeester score was 78+/-32 (normal 14.7). Eighteen patients (64%) had hiatal breakdown, 17 (60%) had wrap failure, 2 (7%) had slipped Nissen, 3 (11%) had paraesophageal hernias, and 1 (3%) had an excessively tight wrap. Twenty-five revisions were completed laparoscopically, while 3 patients required conversion to the open technique. Complications occurred in 9 of 17 (53%) patients failing previous open fundoplications and in 4 of 12 patients (33%) failing previous laparoscopic fundoplications and included 15 gastrotomies and 1 esophagotomy, all repaired laparoscopically, 3 postoperative gastric leaks, and 4 pneumothoraces requiring tube thoracostomy. No deaths occurred. Median length of stay was 5 days (range 2-90 days). At a mean follow-up of 20 months +/- 17, 2 patients (7%) have failed revision of their fundoplications, with the rest of the patients being essentially asymptomatic (93%). CONCLUSIONS: The results achieved with reoperative laparoscopic fundoplication are similar to those of primary laparoscopic fundoplications. Laparoscopic reoperations, particularly of primary open fundoplication, can be technically challenging and fraught with complications.

Simian and human immunodeficiency virus Nef proteins use different surfaces to downregulate class I major histocompatibility complex antigen expression.

Simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) Nef proteins are related regulatory proteins that share several functions, including the ability to downregulate class I major histocompatibility complex (MHC) and CD4 expression on the cell surface and to alter T-cell-receptor-initiated signal transduction in T cells. We compared the mechanisms used by SIV mac239 Nef and HIV-1 Nef to downregulate class I MHC and found that the ability of SIV Nef to downregulate class I MHC requires a unique C-terminal region of the SIV mac239 Nef molecule which is not found in HIV-1 Nef. Interestingly, mutation of the PxxP motif in SIV Nef, unlike in HIV-1 Nef, does not affect class I MHC downregulation. We also found that downregulation of class I MHC by SIV Nef requires a conserved tyrosine in the cytoplasmic domain of the class I MHC heavy chain and involves accelerated endocytosis of class I complexes, as previously found with HIV-1 Nef. Thus, while SIV and HIV-1 Nef proteins use a similar mechanism to downregulate class I MHC expression, they have evolved different surfaces for molecular interactions with cell factors that regulate class I MHC traffic. Mutations in the C-terminal domain of SIV mac239 Nef selectively disrupt class I MHC downregulation, having no detectable effect on other functions of Nef, such as the downregulation of CD4 and CD3 surface expression, the stimulation of SIV virion infectivity, and the induction of SIV replication from T cells infected in the absence of stimulation. The resulting mutants will be useful reagents for studying the importance of class I MHC downregulation for SIV replication and AIDS pathogenesis in infected rhesus macaques.

Two elements target SIV Nef to the AP-2 clathrin adaptor complex, but only one is required for the induction of CD4 endocytosis.

The simian immunodeficiency virus (SIV) and human immunodeficiency virus type 1 (HIV-1) Nef proteins induce the endocytosis of CD4 and class I MHC molecules. Here we show that SIV Nef interacts with the AP-2 adaptor complex via two elements located in the N-terminal region of the Nef molecule, but only the N-distal element is required to induce CD4 endocytosis. This N-distal AP-2 targeting element contains no canonical endocytic signals and probably contacts the AP-2 complex via a novel interaction surface. The data support a model where SIV Nef induces CD4 endocytosis by promoting the normal interactions between the di-leucine sorting signal in the CD4 cytoplasmic domain and AP-2, but does not substitute for the CD4-AP-2 adaptor interaction. Neither element is important for the induction of class I MHC endocytosis, thus indicating that different mechanisms underlie the induction of class I MHC and CD4 endocytosis by Nef. In contrast to SIV Nef, HIV-1 Nef interacts with AP-2 via a surface containing a di-leucine endocytosis signal in the C-terminal disordered loop of Nef. The fact that genetic selection maintains similar molecular interactions via different surfaces in SIV and HIV-1 Nef proteins indicates that these interactions have critical roles for the viral life cycle in vivo.

A two-step reversible-irreversible model can account for a negative activation energy in an Arrhenius plot.

Arrhenius plots of the rate of inactivation (killing) of mammalian cells and Drosophila embryos have "apparent negative" activation energies at low temperatures. This can be explained by assuming that the rate-limiting event resulting in killing is a two-step process or mechanism, where the first step is reversible and the second irreversible. Two examples, consistent with this model, are suggested as possible mechanisms of hypothermic killing: (i) a membrane lipid liquid crystalline-to-gel transition followed by a metabolic block or event which kills the cell and (ii) cold denaturation of a protein followed by protein aggregation.

Recovery of susceptibility following audiogenic seizure in mice.

The rate at which SJL/J mice recover susceptibility following an initial sound-induced seizure was examined. Fewer than 15% of the subjects seized when retested after a 2-min delay, and only 50% reseized after a 10-min delay. The likelihood of a second seizure was enhanced if the initial seizure exhibited a rapid progression to clonus. During the retest, seizures progressed more slowly than during the initial test, which indicates that recovery was not complete even if a second seizure was induced. Finally, recovery of seizure susceptibility was prevented as long as the subject continued to be exposed to intense auditory stimulation following the initial convulsion, an effect previously noted by Alexander and Kopeloff (1980). The findings are discussed in terms of a recently proposed central inhibitory model of the recovery of audiogenic seizure susceptibility.

Somatic and psychological symptoms during isoproterenol-induced panic attacks.

To determine which symptoms characterized isoproterenol-induced panic attacks, we analyzed the presence of panic attacks in 54 panic disorder patients who panicked, 24 patients who did not panic, and 37 controls who did not panic during isoproterenol infusions. The increases over the baseline of the symptoms shortness of breath and fear of going crazy were highly associated with panicking patients when compared to nonpanicking patients and nonpanicking controls. The increases of the symptoms trembling and shaking, generally nervous, and fear of going crazy were highly associated with patients when compared to controls. The possibility of a cognitive theory of panic attacks is discussed.