Impacts of Incubation Delay on the Dynamics of an Eco-Epidemiological System—A Theoretical Study

Parasite and predator play significant role in trophic interaction, productivity and stability of an ecosystem. In this paper, we have studied a host-parasite-predator interaction that incorporates incubation delay. How the qualitative and quantitative behaviors of the system alter with the incubation delay have been discussed both from mathematical and biological point of views. It is observed that for a lower infection rate, the system is stable for all delays; but for a higher infection rate, there exists a threshold value of the delay above which the system is unstable and below which the system is stable leading to the persistence of all the species. Also, the instability arising from the incubation delay may be controlled if somehow the growth rate of predator population is increased. Numerical studies have also been performed to illustrate different analytical findings. Research is supported by UGC, India; F No. 32-173/2006(SR).     

VIRAL HEPATITIS—A Study of Hyperbilirubinemia with Acholuria in Convalescence

In 42 patients convalescing from viral hepatitis, the total and 1-minute serum bilirubin levels were measured on the day bilirubin was first demonstrated to be absent from the urine.The levels of total bilirubin ranged from 0.5 to 6.2 per 100 ml. of blood (mean 2.8 mg.), while the levels of the 1-minute bilirubin ranged from 0.3 to 3.3 mg. per 100 ml. of blood (mean 1.5 mg.).The reason for acholuria in the presence of the elevated 1-minute direct van den Bergh measurements is not clear, but may be due to the failure of the van den Bergh reaction to accurately measure the exact concentrations of free and conjugated bilirubin present in the plasma.     

The Incidence of Japanese Encephalitis in Taiwan—A Population-Based Study

Background

A mass Japanese encephalitis (JE) vaccination program targeting children was launched in Taiwan in 1968, and the number of pediatric JE cases substantially decreased thereafter. The aim of this study was to elucidate the long-term trend of JE incidence, and to investigate the age-specific seroprevalence of JE-neutralizing antibodies.

Methodology/Principal Findings

A total of 2,948 laboratory-confirmed JE cases that occurred between 1966 and 2012 were analyzed using a mandatory notification system managed by the Centers for Disease Control, Taiwan. A total of 6,594 randomly-sampled serum specimens obtained in a nationwide population-based survey in 2002 were analyzed to estimate the seroprevalence of JE-neutralizing antibodies in the general population. The average annual JE incidence rate of the group aged 30 years and older was 0.167 cases per 100,000 people between 2001 and 2012, which was higher than the 0.052 cases per 100,000 people among those aged under 30 years. These seroepidemiological findings indicate that the cohort born between 1963 and 1975, who generally received two or three doses of the vaccine and were administered the last booster dose more than 20 years ago, exhibited the lowest positive rate of JE-neutralizing antibodies (54%). The highest and second highest antibody rates were observed, respectively, in the oldest unvaccinated cohort (86%) and in the youngest cohort born between 1981 and 1986, who received four doses 10–15 years ago (74%).

Conclusion/Significance

Over the past decade, the main age group of the confirmed JE cases in Taiwan shifted from young children to adults over 30 years of age. People who were born between 1963 and 1975 exhibited the lowest seroprevalence of JE-neutralizing antibodies. Thus, the key issue for JE control in Taiwan is to reduce adult JE cases through a cost-effective analysis of various immunization strategies.     

THE POSTPHLEBITIC SYNDROME—A Study of Possible Factors in Subjective Disability

Three hundred patients with the post-thrombophlebitic syndrome were studied. The lower extremities were involved in the majority of cases. Severe disabling subjective symptoms, such as burning, aching, cramping and shooting pains, occurred in approximately 15 per cent of cases regardless of the presence or absence of objective findings such as ulcerations, edema or dermatitis. Subjective symptoms occurred in about as many men as women. The persistence and severity of disabling subjective symptoms seemed to be unrelated to the possibility of compensation or pecuniary gain. No adequate explanation could be found for the perseverance of disabling subjective symptoms. There was no consistent relation of subjective symptoms and disability to psychic factors.     

RUBELLA ARTHRITIS—A Study of Twenty Cases

Twenty patients, five males and fifteen females, who had rubella arthritis were observed for periods ranging from one to ten years after recovery.Rubella arthritis in these patients was characterized by polyarthritis associated with fibrositis, myalgia, paresthesias and muscular weakness. All of the male patients but only one-third of the females had involvement of the knee joints. The small joints of the hands were the joints most commonly affected in women. Post-rubella arthritis rheumatic symptoms, especially fibrositis, persisted for many months in almost half of the females, not at all in the males.The leukocyte content of the blood tended to be low and the erythrocyte sedimentation rate accelerated in the few patients in which determinations were done.Latex tests were performed in 17 patients. Ten of the 17 were studied with the three-stage technique of Hall. Results of inhibition tests were positive in 80 per cent of the patients with rubella arthritis studied who were tested within 18 months after the onset of illness. None of the patients tested 18 months or more after rubella arthritis had positive reaction.     

Molecular Dynamics of Class A β-lactamases—Effects of Substrate Binding

The effects of substrate binding on class A β-lactamase dynamics were studied using molecular dynamics simulations of two model enzymes; 40 100-ns trajectories of the free and substrate-bound forms of TEM-1 (with benzylpenicillin) and PSE-4 (with carbenicillin) were recorded (totaling 4.0 μs). Substrates were parameterized with the CHARMM General Force Field. In both enzymes, the Ω loop exhibits a marked flexibility increase upon substrate binding, supporting the hypothesis of substrate gating. However, specific interactions that are formed or broken in the Ω loop upon binding differ between the two enzymes: dynamics are conserved, but not specific interactions. Substrate binding also has a global structuring effect on TEM-1, but not on PSE-4. Changes in TEM-1’s normal modes show long-range effects of substrate binding on enzyme dynamics. Hydrogen bonds observed in the active site are mostly preserved upon substrate binding, and new, transient interactions are also formed. Agreement between NMR relaxation parameters and our theoretical results highlights the dynamic duality of class A β-lactamases: enzymes that are highly structured on the ps-ns timescale, with important flexibility on the μs-ms timescale in regions such as the Ω loop.     

Coexistence of Probe Conformations in Lipid Phases—A Polarized Fluorescence Microspectroscopy Study

Several well-established fluorescence methods depend on environment-sensitive probes that report about molecular properties of their local environment. For reliable interpretation of experiments, careful characterization of probes’ behavior is required. In this study, bleaching-corrected polarized fluorescence microspectroscopy with nanometer spectral peak position resolution was applied to characterize conformations of two alkyl chain-labeled 7-nitro-2-1,3-benzoxadiazol-4-yl phospholipids in three model membranes, representing the three main lipid phases. The combination of polarized and spectral detection revealed two main probe conformations with their preferential fluorophore dipole orientations roughly parallel and perpendicular to membrane normal. Their peak positions were separated by 2–6 nm because of different local polarities and depended on lipid environment. The relative populations of conformations, estimated by a numerical model, indicated a specific sensitivity of the two probes to molecular packing with cholesterol. The coexistence of probe conformations could be further exploited to investigate membrane organization below microscopy spatial resolution, such as lipid rafts. With the addition of polarized excitation or detection to any environment-sensitive fluorescence imaging technique, the conformational analysis can be directly applied to explore local membrane complexity.     

Traffic Deaths—A Preliminary Study of Urban and Rural Fatalities in California

An analysis by the California Department of Public Health of California Highway Patrol reports for 1961 showed that traffic accidents injured one and one-half times as many people per 1,000 population in rural California counties (under 50,000 people) as in urban counties (over 500,000 people), also persons injured in rural counties were almost four times as likely to die of their injuries as those injured in urban counties.A death certificate study was undertaken of 782 traffic deaths (excluding pedestrians) occurring in rural and urban California counties during 1961. Accidents occurring in rural counties tended to be single vehicle accidents which resulted in less severe injuries, while those in urban counties tended to be two vehicle and multiple vehicle accidents resulting in more serious injuries. The anatomic distribution of injuries was the same for both urban and rural accidents. However, people dying in rural accidents more frequently died at the scene of the accident, died sooner after injury, and died of less serious injuries than did those injured in urban accidents. For injuries where theoretically few lives should be salvaged by prompt emergency care, the time between injury and death was about the same in urban as in rural counties. Where such care should delay or prevent death because the injury was possibly or probably salvageable, those injured in rural counties died more quickly.Thirty-two per cent of fatalities in rural counties happened to urban and out-of-state residents, while only 12 per cent of fatalities in urban counties were to rural or out-of-state residents, suggesting that traffic accidents to non-residents may place an excessive load upon medical care resources in rural areas.     

Medulloblastoma—Treatment and Prognosis A Study of Seventeen Cases in Ten Years

In a series of 17 biopsy-proved cases of medulloblastoma all patients were treated by megavoltage irradiation in the Stanford University Division of Radiation Therapy. The entire craniospinal axis was treated in each case. The five-year survival in the series was 27 percent.Two ten-year survivors were studied in detail. The major longterm disability was inhibition of growth of the vertebral column.In this series, a normal tissue nominal standard dose of at least 1275 rets was necessary for tumor control.     

Disturb or Stabilize? A Molecular Dynamics Study of the Effects of Resorcinolic Lipids on Phospholipid Bilayers

Resorcinolic lipids, or resorcinols, are commonly found in plant membranes. They consist of a substituted benzene ring forming the hydrophilic lipid head, attached to an alkyl chain forming the hydrophobic tail. Experimental results show alternative effects of resorcinols on lipid membranes. Depending on whether they are added to lipid solutions before or after the formation of the liposomes, they either stabilize or destabilize these liposomes. Here we use atomistic molecular dynamics simulations to elucidate the molecular nature of this dual effect. Systems composed of either one of three resorcinol homologs, differing in the alkyl tail length, interacting with dimyristoylphosphatidylcholine lipid bilayers were studied. It is shown that resorcinols preincorporated into bilayers induce order within the lipid acyl chains, decrease the hydration of the lipid headgroups, and make the bilayers less permeable to water. In contrast, simulations in which the resorcinols are incorporated from the aqueous solution into a preformed phospholipid bilayer induce local disruption, leading to either transient pore formation or even complete rupture of the membrane. In line with the experimental data, our simulations thus demonstrate that resorcinols can either disturb or stabilize the membrane structure, and offer a detailed view of the underlying molecular mechanism.     

Long Route or Shortcut? A Molecular Dynamics Study of Traffic of Thiocholine within the Active-Site Gorge of Acetylcholinesterase

The principal role of acetylcholinesterase is termination of nerve impulse transmission at cholinergic synapses, by rapid hydrolysis of the neurotransmitter acetylcholine to acetate and choline. Its active site is buried at the bottom of a deep and narrow gorge, at the rim of which is found a second anionic site, the peripheral anionic site. The fact that the active site is so deeply buried has raised cogent questions as to how rapid traffic of substrate and products occurs in such a confined environment. Various theoretical and experimental approaches have been used to solve this problem. Here, multiple conventional molecular dynamics simulations have been performed to investigate the clearance of the product, thiocholine, from the active-site gorge of acetylcholinesterase. Our results indicate that thiocholine is released from the peripheral anionic site via random pathways, while three exit routes appear to be favored for its release from the active site, namely, along the axis of the active-site gorge, and through putative back- and side-doors. The back-door pathway is that via which thiocholine exits most frequently. Our results are in good agreement with kinetic and kinetic-crystallography studies. We propose the use of multiple molecular dynamics simulations as a fast yet accurate complementary tool in structural studies of enzymatic trafficking.     

Scrub Typhus Meningitis in South India — A Retrospective Study

Background

Scrub typhus is prevalent in India although definite statistics are not available. There has been only one study on scrub typhus meningitis 20 years ago. Most reports of meningitis/meningoencephalitis in scrub typhus are case reports

Methods

A retrospective study done in Pondicherry to extract cases of scrub typhus admitted to hospital between February 2011 and January 2012. Diagnosis was by a combination of any one of the following in a patient with an acute febrile illness- a positive scrub IgM ELISA, Weil-Felix test, and an eschar. Lumbar puncture was performed in patients with headache, nuchal rigidity, altered sensorium or cranial nerve deficits.

Results

Sixty five cases of scrub typhus were found, and 17 (17/65) had meningitis. There were 33 males and 32 females. Thirteen had an eschar. Median cerebrospinal fluid (CSF) cell count, lymphocyte percentage, CSF protein, CSF glucose/blood glucose, CSF ADA were 54 cells/µL, 98%, 88 mg/dL, 0.622 and 3.5 U/mL respectively. Computed tomography was normal in patients with altered sensorium and cranial nerve deficits. Patients with meningitis had lesser respiratory symptoms and signs and higher urea levels. All patients had received doxycycline except one who additionally received chloramphenicol.

Conclusion

Meningitis in scrub typhus is mild with quick and complete recovery. Clinical features and CSF findings can mimic tuberculous meningitis, except for ADA levels. In the Indian context where both scrub typhus and tuberculosis are endemic, ADA and scrub IgM may be helpful in identifying patients with scrub meningitis and in avoiding prolonged empirical antituberculous therapy in cases of lymphocytic meningitis.     

ENDOMETRIOSIS—A Clinical and Pathological Study of 219 Cases

One hundred twenty-four cases of external endometriosis and 95 cases of adenomyosis were analyzed. The two are clinically different diseases which have one feature in common—a reactive fibrosis to aberrant endometrial tissue. They are coexistent in about the same frequency as would result from a noncausal relationship.The origin of external endometriosis from the epithelial “inclusion” cyst is considered proven histologically. This is the source of origin of most external endometriosis, although occasional involvement from regurgitated endometrium probably occurs. Both the endometrial and the serous cysts have a common parentage in this anlage.Certain histological features that are considered pathognomonic of endometriosis are: (1) the minimal lesion, (2) the characteristic cuboidal lined cyst, (3) the siderophagic cyst without lining, and (4) the siderophagic nest.Recognition of the siderophagic nest will permit identification of extinct endometriosis and thus aid in studies to determine the spontaneous or therapeutically induced regression of the disease.The coexistence of endometriosis with other pelvic pathological changes, notably carcinoma, indicates the need for further studies to search the possibility of relationship.The ability of ectopic deposits of endometrium to become malignant on rare occasions would appear to be proven, but it is a rare occurrence and there is no justification for regarding endometriosis as a premalignant disease.