The Neuroimmunology of Multiple Sclerosis: Possible Roles of T and B Lymphocytes in Immunopathogenesis

Multiple sclerosis (MS) is an inflammatory disease of the central nervous system white matter. The association of the disease with MHC genes, the inflammatory white matter infiltrates, similarities with animal models, and the observation that MS can be treated with immunomodulatory and immunosuppressive therapies support the hypothesis that autoimmunity plays a major role in the disease pathology. Evidence supports activated CD4⁺ myelin-reactive T cells as major mediators of the disease. In addition, a renewed interest in the possible contribution of B cells to MS immunopathology has been sparked by nonhuman primate and MS pathological studies. This review focuses on the immunopathology of MS, outlining the hypothetical steps of tolerance breakdown and the molecules that play a role in the migration of autoreactive cells to the CNS. Particular focus is given to autoreactive T cells and cytokines as well as B cells and autoantibodies and their role in CNS pathogenesis in MS.     

Polysomnographic and actigraphic evidence of sleep fragmentation in patients with irritable bowel syndrome

STUDY OBJECTIVE: To characterize the function and quality of sleep in patients with irritable bowel syndrome (IBS). DESIGN: A prospective study with a historic comparison group. SETTING: A regional hospital that also serves as a tertiary referral center. PATIENTS: Eighteen patients with IBS and a comparison group of 20 matched adults with mild benign snoring. INTERVENTIONS: A polysomnography study and a wrist actigraphy study. MEASUREMENTS: All subjects underwent sleep studies and completed self-report questionnaires (IBS severity, psychosocial variables, sleep function, and Epworth Sleepiness Scale). Fourteen IBS and 11 comparison patients underwent actigraphy. RESULTS: The IBS patients had more than 70% less slow-wave stage sleep (4.5 +/- 7.3% vs 19.3 +/- 12.9%; P = 0.006), compensated by increased stage 2 sleep (72.2 +/- 6.6% vs 60.1 +/- 16.8%; P = 0.01). The IBS group had significant sleep fragmentation with a significantly higher arousal and awakening index (P < 0.001), a longer wake period after sleep onset (P = 0.02), and more downward shifts to lighter sleep stages (P = 0.01). The 4-night actigraphy study supported the polysomnography findings. The sleep fragmentation index was significantly higher (P = 0.008) in the IBS group. The IBS patients reported greater daytime sleepiness (9.0 +/- 4.8 vs 6.4 +/- 4.8, Epworth Sleepiness Scale score, P < 0.01) and greater impairment in quality of life, which correlated significantly with the sleep fragmentation indexes. The difference between the groups was not due to differences in baseline anxiety/depression levels. CONCLUSIONS: Patients with IBS have impaired sleep quality, reduced slow-wave sleep activity, and significant sleep fragmentation. The cause-and-effect relationship of these findings with patients' daytime symptoms should be studied further.     

Risk factors,clinical course and outcomes of pregnancy-related group A streptococcal infections: retrospective 13-year cohort study

Objectives

To investigate the incidence, risk factors, clinical course and outcomes of pregnancy-related group A streptococcus (GAS) infection.

Stress-induced analgesia: adaptive pain suppression

In this paper we have examined the phenomenon of stress-induced analgesia. We have described the procedures used to measure analgesia and have suggested that the tests can be designed not only to indicate changes in pain threshold but also to allow for the determination of the capacity to execute adaptive behavior. Aside from enabling the analysis of responses, tests that induce reflexive as well as nonreflexive behavior may have the capacity to separate the more complex aspects of pain such as the possible presence of two components of pain, sensory/discriminative and motivational/affective. These components may be of fundamental importance for any attempt to understand the biological significance of SIA. Our examination of the neurotransmitter and neuropeptide systems has revealed that they are affected by the same manipulations that induce SIA. These amines and perhaps peptides play an integral role in learning, motivation, and performance. We conclude that the functional advantage of a reduction of pain during stressful situations is significant because it allows the animal to react in threatening and perhaps critical situations as if there were no pain. Once the pain system is inhibited, other systems modulate and mediate adaptive responses that expedite the survival of the animal.     

Does ICSI affect early serum beta-HCG in pregnancies achieved after IVF?

This study was conducted to compare early serum human chorionic gonadotrophin (HCG) concentrations in singleton pregnancies achieved after intracytoplasmic sperm injection (ICSI), with those achieved after conventional in-vitro fertilization (IVF). Early serum HCG, 14-16 days after embryo transfer, was analysed in 99 IVF pregnancies achieved after ICSI (group A), and compared to 105 conventional IVF pregnancies (group B). All women were treated at the IVF Unit, Lis Maternity Hospital. Records were studied retrospectively. The mean +/- SE serum HCG concentration on day 14 after embryo transfer in group A was 190.5 +/- 17.4 mIU/ml, compared to 195.7 +/- 14.03 mIU/ml in group B. HCG concentration 14 days after embryo transfer in both groups A and B was higher in women with mechanical factor than in couples with male factor infertility or unexplained infertility (246 +/- 31.4, 183.3 +/- 16.4, 177.98 +/- 14.3 mIU/ml respectively). On the 16th day after embryo transfer, the HCG concentration increased, and the difference between the groups was maintained. Only in the subgroup of unexplained infertility did we find a difference in concentrations of HCG between ICSI and conventional IVF: on the 16th day following embryo transfer in this group there was a significant difference in HCG concentrations (395. 8 +/- 21 and 545.6 +/- 45.7 respectively; P = 0.04). HCG concentrations did not differ overall in the conventional IVF pregnancies compared with those achieved by ICSI. However, a statistical difference in early serum HCG concentrations was found in relation to the aetiology of infertility.     

Cytokine induction of heat shock protein in human granulosa-luteal cells

The infiltration of leukocytes is a characteristic feature ofluteolysis in humans. Leukocytes are known to generate physiologicalinducers of cell stress such as cytokines which have been implicatedas mediators of functional luteal regression. In cells exposedto stress, a response characterized by an increase in heat shockprotein (HSP) synthesis occurs. Recently, the induction of HSP-70in rat luteal cells has been shown to inhibit luteinizing hormone(LH) and cAMP-sensitive progesterone production, possibly byinterfering with the translocation of cholesterol to the mitochondrialcytochrome P450_SCC. We therefore investigated whether HSP-70is induced in human granulosa-luteal cells and its relationshipto steroidogenesis. [³⁵S]Methionine labelling showed an increasein a 70 kDa protein after heat treatment which was demonstratedto be HSP-70 by Western analysis using monoclonal antibodiesagainst the constitutive and inducible forms of HSP-70. Inductionof HSP-70 in human granulosa-luteal cells was also seen withinterferon (IFN) (10 ng/ml), tumour necrosis factor (TNF)-     

Shifting US Patterns of COVID-19 Mortality by Race and Ethnicity From June–December 2020

ObjectivesThe COVID-19 pandemic has disproportionately affected racial and ethnic minorities in the United States and has been devastating for residents of nursing homes (NHs). However, evidence on racial and ethnic disparities in COVID-19–related mortality rates within NHs and how that has changed over time has been limited. This study examines the impact of a high proportion of minority residents in NHs on COVID-19–related mortality rates over a 30-week period.DesignLongitudinal study.Setting and ParticipantsCenters for Medicare & Medicaid Services Nursing Home COVID-19 Public Use File data from 50 states from June 1, 2020, to December 27, 2020.MethodsWe linked data from 11,718 NHs to (1) Nursing Home Compare data, (2) the Long-Term Care: Facts on Care in the U.S., and (3) US county-level data on COVID cases and deaths. Our primary independent variable was proportion of minority residents (blacks and Hispanics) in NHs and its association with mortality rate over time.ResultsDuring the first 6 weeks from June 1, 2020, NHs with a higher proportion of black residents reported more COVID-19 deaths per 1000 followed by NHs with a higher proportion of Hispanic residents. Between 7 and 12 weeks, NHs with a higher proportion of Hispanic residents reported more deaths per 1000, followed by NHs with a higher proportion of black residents. However, after 23 weeks (mid-November 2020), NHs serving a higher proportion of white residents reported more deaths per 1000 than NHs serving a high proportion of black and Hispanic residents.Conclusions and ImplicationsThe disparities in COVID-19–related mortality for nursing homes serving minority residents is evident for the first 12 weeks of our study period. Policy interventions and the equitable distribution of vaccine are required to mitigate the impact of systemic racial injustice on health outcomes of people of color residing in NHs.