Definition and epidemiology of mild traumatic brain injury.

BACKGROUND/OBJECTIVES: The definition of mild traumatic brain injury (mTBI), also known as concussion, has been a matter of controversy, which makes comparison between studies difficult. Incidence varies greatly from one country to another. The present article reviews definitions and epidemiology. METHODS: Literature review. RESULTS: According to the Mild TBI Committee of the American Congress of Rehabilitation Medicine, revised by the World Health Organization (WHO), mTBI is defined by a Glasgow Coma Scale score between 13 and 15 at 30minutes post-injury, and one or more of the following symptoms: <30min loss of consciousness; <24hours post-traumatic amnesia (PTA); impaired mental state at time of accident (confusion, disorientation, etc.); and/or transient neurological deficit. If a focal lesion is found on computed tomography (CT) or magnetic resonance imaging (MRI), the term "complicated mild TBI" has been proposed. Incidence of mTBI is 200-300/100,000 persons per year for hospitalized patients and probably twice as high if non-hospitalized patients are included. However, a few recent population-based studies reported a much higher rate (>700/100,000). A changing pattern of epidemiology has been found in high-income countries, related to a decrease in road-accident injuries in young adults, while conversely the proportion of falls has increased with population aging. CONCLUSION: Mild TBI is a major public health concern, the epidemiology of which has greatly changed in the last twenty years.

The anatomy of the musculocutaneous latissimus dorsi flap for neophalloplasty.

In transgender surgery, the ideal neophallus is one that: (a) is constructed using a reproducible procedure, (b) possesses tactile and erogenous sensation, (c) is large and rigid enough (naturally, or using a prosthesis) to permit penetrative intercourse, (d) leaves acceptable donor site morbidity, (e) results in esthetically satisfactory appearance, and (f) allows for voiding while standing. The musculocutaneous latissimus dorsi (MLD) flap has favorable results in the area of neophalloplasty. Among its advantages are acceptable donor site appearance, stiffness sufficient for intercourse, and esthetically satisfactory genital appearance. The anatomy of the MLD flap supports the creation of a neophallus for transsexual anatomy revision. Herein, we give an overview of the advantages and disadvantages of the procedure, and the anatomical details and surgical steps involved. Novel illustrations were created from standard surgical text descriptions to clarify this topic for surgical training and patient understanding and decision making. A review of the relevant literature regarding the anatomy, procedure development, and outcomes is presented. The MLD flap uses part of the latissimus dorsi muscle with branches of the thoracodorsal vessels and nerve to construct a neophallus. A thin strip of muscle around the pedicle is harvested, resulting in a slightly curvilinear scar. The blood supply is connected to the femoral artery and saphenous vein or the deep inferior epigastric artery and vein, while the nerve is connected to the ilioinguinal nerve or the obturator nerve. The MLD flap for neophalloplasty is a reliable graft with a well concealed scar and low donor site morbidity. Clin. Anat. 31:152-159, 2018. © 2017 Wiley Periodicals, Inc.

Quantitative determination of residual active pharmaceutical ingredients and intermediates on equipment surfaces by ion mobility spectrometry.

Ion mobility spectrometry (IMS) is an analytical technique that separates ions based on their gas phase mobility at atmospheric pressure. Since gas phase ion mobility is a function of the shape and structure of the ion, this technique has the potential to provide unique specificity and selectivity. Furthermore, IMS is very sensitive (subnanogram detection limits for many small molecules), and a single analysis is typically completed within 1 min. In principle, these features of IMS should make it an ideal choice for use in cleaning verification analysis of pharmaceutical manufacturing equipment. This report describes the successful development and validation of three different equipment cleaning verification methods using IMS. The methods were developed for a specific intermediate (Compound A) in the synthetic route for a drug substance as well as for final drug substances (active pharmaceutical ingredients Compounds B and C). The cleaning verification methods were validated with respect to specificity, linearity, precision, accuracy, stability, and limit-of-quantitation. In all cases, the limits-of-quantitation were determined to be at the nanogram or sub-nanogram level. Both swab and rinse samples collected from the equipment surfaces were successfully analyzed and manufacturing equipment down-time was significantly minimized due to the reduction in cleaning verification analysis time (for example, the total analysis time for more than 30 samples using IMS was reduced to less than 2h).

Cellular origins of beta-cell regeneration: a legacy view of historical controversies.

Beta-cell regeneration represents a major goal of therapy for diabetes. Unravelling the origin of beta cells during pancreatic regeneration could help restore a functional beta-cell mass in diabetes patients. This scientific question has represented a longstanding interest still intensively investigated today. This review focuses on pioneering observations and subsequent theories made 100 years ago and describes how technical innovation helped resolve some, but not all, of the controversies generated by these early investigators. At the end of the 19th century, complete pancreatectomy demonstrated the crucial physiological role of the pancreas and its link with diabetes. Pancreatic injury models, including pancreatectomy and ductal ligation, allowed investigators to describe islet function and to assess the regenerative capacity of the pancreas. Three main theories were proposed to explain the origins of newly formed islets: (i) transdifferentiation of acinar cells into islets, (ii) islet neogenesis, a process reminiscent of islet formation during embryonic development, and (iii) replication of preexisting islet cells. Despite considerable technical innovation in the last 50 years, the origin of new adult beta cells remains highly controversial and the same three theories are still debated today.

Frequency and severity of vasomotor symptoms among peri- and postmenopausal women in the United States.

OBJECTIVE: To describe characteristics of vasomotor symptoms, specifically daily frequency and severity, among women 40-65 years old in the United States (US). DESIGN: A survey was completed by a nationally representative sample of 4402 US women aged 40-65 years old. A questionnaire focusing on menopausal symptoms was administered online in April 2005. RESULTS: The prevalence of vasomotor symptoms was 79% in peri- and 65% in postmenopausal women. Women with daily vasomotor symptoms had an average of 2.5 very mild/mild, 2.6 moderate, 2.5 severe, and 1.4 very severe daytime hot flushes in a typical day. Women with night sweats every night had an average of 2.4 moderate, 3.2 severe, and 2.7 very severe night sweats in a typical night. Overall, 9% of peri- and 7% of postmenopausal women reported 7+ moderate to very severe vasomotor symptoms in a typical day. Although some women reported that symptoms were worse in the evening and in the summer, many women reported they were consistent, both throughout the day and throughout the seasons of the year. CONCLUSIONS: The Menopause Epidemiology Study builds upon existing literature by providing data on daily frequency and severity of vasomotor symptoms. There are many women with frequent and severe vasomotor symptoms who may benefit from treatment.

Gene flow in cherry orchards.

A survey of Australian cherry orchards identified the cherry cultivars Sunburst, Summit, Merchant, Sam, Sylvia, Tieton, Kordia, Regina, Empress, Nordwunder and Ulster as having low fruit-set associated with poor pollination. Unique orchard sites across Australia where low fruit-set was not a problem for these cultivars were located, and pollen gene-flow-analysis conducted using 6-PGD, GOT, G6PD, GPI, IDH, FDP and SKDH isozyme markers. Pollenisers for the above-mentioned cultivars were determined and Stella was a polleniser for eight of them. Stella's predominance was linked to it reaching full bloom before the other cultivars; anther dehiscence occurs sometime after flowers open, as such newly opened flowers; the most-fertile stage was mainly exposed to Stella pollen. Sunburst a self-compatible cultivar showed no evidence of self-fertilisation. The majority of pollenisers were found to be within 20 m of the tree under examination. Isozyme profiles for 22 cultivars not previously analysed are also presented.

Ginkgo biloba precipitating epileptic seizures.

BACKGROUND: The herbal remedy Ginkgo biloba is promoted as a treatment for a variety of ailments including memory loss and dementia, poor concentration and mood, glaucoma, 'cerebral insufficiency' and 'peripheral circulatory disturbances'. It is gaining worldwide popularity, particularly as a potential treatment for dementia. CASE REPORTS: Two patients with well-controlled epilepsy presented with recurrent seizures within 2 weeks of commencing extract of Ginkgo biloba. The herbal remedy was discontinued and both patients are seizure-free several months later. DISCUSSION: Ginkgo biloba may have precipitated seizures in these two patients. This and other potential adverse effects should be highlighted on the packaging of the drug.

Increased first-contact rates for very-late-onset schizophrenia-like psychosis in African- and Caribbean-born elders.

BACKGROUND: Studies have consistently shown a higher incidence of schizophrenia with onset in early adult life in African and Caribbean migrants to the UK. AIMS: To establish the incidence (first-contact rates) of very-late-onset (>60 years) schizophrenia-like psychosis (SLP) in south London and to test the hypothesis that this is higher among African- and Caribbean-born than indigenous elders. METHOD: We identified all new referrals of SLP to the Maudsley Hospital between 1995 and 2000. Demographic details, including age, ethnicity and electoral ward (address), were obtained from case notes. Incidence was estimated using 1997 census data to determine the denominator population for each ethnic group. RESULTS: The incidence of SLP was significantly higher in African- and Caribbean-born than indigenous elders: 172.4 per 100,000 population (95% CI=57.9--286.8) in African- and Caribbean-born males and 323.5 per 100,000 population (95% CI 167.8--479.1) in African- and Caribbean-born females. Rates also were increased in elders from other immigrant groups, but the numbers involved were too small to reach accepted levels of significance. CONCLUSIONS: Large-scale epidemiological studies are needed to determine both the incidence of and the coexistent risk factors for SLP among all elderly migrants, who may constitute a group with high service needs.

Review of the role of progesterone in the management of postnatal mood disorders.

Postnatal mood disorders (maternity blues, postnatal depression and puerperal psychosis) are cross-cultural symptoms that are commonly seen in primary care by general practitioners and midwives, by gynecologists and obstetricians, and within the psychiatric services. One of several hypotheses for their causation is falling progesterone levels in the postpartum period. Progesterone supplements are therefore currently used in the treatment of postnatal mood disorders, both in primary and secondary health care settings. The evidence for this is reviewed. The MEDLINE and PSYCHLIT databases from 1966 to 1999 were searched. References reporting observational data on progesterone levels around delivery or therapeutic studies using progesterone were retrieved. Additional references were identified by citation tracking from these and direct contact with available authors. Eight papers were identified. Although there is some weak evidence for its role in maternity blues and some theoretical justification for its use, there is no robust primary research to support the use of progesterone in the treatment of postnatal mood disorders. Progesterone is being used to prevent recurrence of postnatal depression but the evidence supporting its efficacy is lacking. Its use in the treatment of postnatal mood disorders cannot be recommended on the basis of current evidence. Randomized controlled trials are needed to decide if it has a role in the treatment and prevention of postnatal mood disorders.

Multiple meningiomas: case report and review of the literature.

A case of a 69 year old woman with multiple meningiomas is presented. Since her first presentation with Jacksonian seizures in 1978, she has had 16 meningiomas excised in seven separate surgical procedures. This is extremely unusual due to both the large number of tumours, and the long period over which they have occurred. We review the epidemiology, possible pathogenesis and genetic associations of this condition.

Isolation and characterization of fission yeast sns mutants defective at the mitosis-to-interphase transition.

pim1-d1ts was previously identified in a visual screen for fission yeast mutants unable to complete the mitosis-to-interphase transition. pim1+ encodes the guanine nucleotide exchange factor (GEF) for the spi1 GTPase. Perturbations of this GTPase system by either mutation or overproduction of its regulatory proteins cause cells to arrest with postmitotic condensed chromosomes, an unreplicated genome, and a wide medial septum. The septation phenotype of pim1-d1ts was used as the basis for a more extensive screen for this novel class of sns (septated, not in S-phase) mutants. Seventeen mutants representing 14 complementation groups were isolated. Three strains, sns-A3, sns-A5, and sns-A6, representing two different alleles, are mutated in the pim1+ gene. Of the 13 non-pim1ts sns complementation groups, 11 showed genetic interactions with the spi1 GTPase system. The genes mutated in 10 sns strains were synthetically lethal with pim1-d1, and six sns strains were hypersensitive to overexpression of one or more of the known components of the spil GTPase system. Epistasis analysis places the action of the genes mutated in nine of these strains downstream of pim1+ and the action of one gene upstream of pim1+. Three strains, sns-A2, sns-B1, and sns-B9, showed genetic interaction with the spil GTPase system in every test performed. sns-B1 and sns-B9 are likely to identify downstream targets, whereas sns-A2 is likely to identify upstream regulators of the spi1 GTPase system that are required for the mitosis-to-interphase transition.

Inheritance and linkage of isozymes in sweet cherry (Prunus avium L.).

Eight polymorphic isozyme loci, 6PGD, G6PD, MDH, PGM, SKDH, FDP, GOT and IDH, in sweet cherry where found to be in one linkage group, with a ninth isozyme locus, GPI, being in another linkage group on a different chromosome. Isozymes were also linked to the incompatibility S locus and this explained the disturbed segregation ratios observed in the first generation from controlled hybridisations between different sweet cherry cultivars. Analysis revealed close linkage between the isozyme and S loci. The results supported a pre-existing theory that the S gene in cherry consists of three linked segments each coding for a different function. Progeny derived from selfing of Stella, the self-fertile cherry cultivar, also showed disturbed segregation ratios and an absence of homozygotes for the isozyme loci assayed. This demonstrated that codominant inheritance of the S alleles had not been effected by the self-fertile mutation.

The thrombin receptor in human platelets is coupled to a GTP binding protein of the G alpha q family.

The thrombin receptor is a G protein-coupled receptor, but the G proteins functionally coupled to this receptor in human platelets are not yet definitively identified. Thrombin stimulation of platelets leads to phospholipase C-mediated increases in intracellular calcium, and previous studies have suggested that the thrombin receptor is coupled to members of the Gq family. We now demonstrate direct GTPase activation by thrombin receptor activation peptide (TRAP) in human platelet membranes, and specific inhibition of TRAP-activated GTPase by antibodies to Gq. These data demonstrate functional coupling of the thrombin receptor to a member of the Gq family.

Multiple beam generation using a stratified volume holographic grating.

The parameters of several stratified volume holographic gratings are optimized in order to obtain high diffraction efficiency beam spliters. Two-, three-, five-, seven-, and nine-beam fan-outs are theoretically studied and compared with what has been achieved by other means. With a simple optical setup, a fan-out element that generates seven beams of equal intensity is experimentally realized and a comparison with theory is made.

Sweet cherry cultivar identification by leaf isozyme polymorphism.

Isozyme polymorphism can assist in the identification of cherry cultivars. Ten isozymes, each showing variation at only one locus, provide 70 unique genotype profiles from leaf extracts of 78 different sweet cherry cultivars. Polymorphism in 6PGD, G6PD, GPI, IDH, PGM, FDP, SKDH and PER is demonstrated for the first time, while observations are extended for the previously described polymorphisms in MDH and GOT. Some cultivars with identical morphological characters and previously treated as one cultivar can be separated on the basis of isozyme genotype. Irradiated mutants and parent material could also be differentiated.

Acquired resistance and granuloma formation in experimental visceral leishmaniasis. Differential T cell and lymphokine roles in initial versus established immunity.

In naive BALB/c mice, acquisition of resistance to Leishmania donovani and formation of antileishmanial tissue granulomas are linked expressions that require both L3T4+ and Lyt 2+ cells as well as both IL-2 and IFN-gamma. To determine the mechanisms of established resistance to L. donovani, rechallenged immune BALB/c mice were treated with T cell- and lymphokine-depleting mAb or cyclosporin A. In the liver, resistance to rechallenge was inhibited by treatment with anti-Lyt 2 but not anti-L3T4 mAb. Resistance was also impaired by anti-IL-2 treatment but not by anti-IFN-gamma mAb. The hepatic granulomatous response to rechallenge, however, was not impaired by either anti-Lyt 2 or anti-IL-2 mAb nor by anti-L3T4 or anti-IFN-gamma treatment. In contrast, cyclosporin A suppressed granuloma formation but not antileishmanial activity. These results indicate a particularly important antileishmanial host defense role for Lyt 2+ cells and IL-2 in sensitized animals, and when compared to prior observations in L. donovani-infected naive mice, suggest that 1) discrete T cell- and lymphokine-dependent mechanisms are involved in initial acquisition of resistance vs established immunity, 2) more than one mechanism can mediate the development of tissue granulomas, and 3) granuloma formation by itself may not be required nor necessarily sufficient to confer antimicrobial activity.

Gamma interferon-activated human macrophages and Toxoplasma gondii, Chlamydia psittaci, and Leishmania donovani: antimicrobial role of limiting intracellular iron.

Iron-saturated transferrin did not reverse the intracellular killing or inhibition of Toxoplasma gondii, Chlamydia psittaci, or Leishmania donovani by gamma interferon-activated human macrophages. Deferoxamine, an iron chelator, also did not impair replication within unstimulated macrophages. Limiting the availability of intracellular iron is an unlikely mechanism in human macrophage activity against these three diverse pathogens.

Response to chemotherapy in experimental visceral leishmaniasis: T cell-dependent but interferon-gamma- and interleukin-2-independent.

The capacity of Leishmania donovani-infected BALB/c mice to respond to conventional chemotherapy with pentavalent antimony (Sb) is T cell dependent and, in nude mice, can be restored in part by treatment with the T cell lymphokines, interferon-gamma (IFN-gamma) or interleukin-2 (IL-2). To document the presumed role of endogenous IFN-gamma and IL-2 in responsiveness to antileishmanial chemotherapy in the T cell-intact host, L. donovani-infected euthymic BALB/c mice were treated with anti-IFN-gamma or anti-IL-2 monoclonal antibodies (MAbs) before and after Sb administration. Treatment with MAbs exacerbated visceral infection but did not inhibit the in vivo efficacy of Sb. Thus, while combination therapy of Sb plus IFN-gamma or IL-2 may prove beneficial in T cell-deficient hosts with visceral leishmaniasis, T cell activities other than or in addition to IFN-gamma or IL-2 production may mediate in vivo responsiveness to antileishmanial chemotherapy in the euthymic host.

Effects of breed and wintering diet on heifer postweaning growth and development.

Fifteen spring-born Angus (AN) and 25 Brangus (BN) weanling heifers were used in a 2x5 factorial arrangement of treatments to evaluate the effects of breed and postweaning winter diet on heifer growth and development. Dietary treatments were warm-season perennial grass hay (H), ammoniated H (AH), H plus .68 kg/d cottonseed meal (HP), H plus .45 kg/d cottonseed meal plus 1.37 kg/d ground corn (HPE) and HPE plus 200 mg/d monensin (HPEM). Mean initial weight and age for the 107-d feed trial were 207 kg and 270 d. Brangus had .06 kg greater (P less than .05) ADG than AN during the trial. Although digestible DM intake (DDMI) relative to body weight was greater (P less than .10) for AN than for BN, ADG:DDMI was greater (P less than .05) for BN than for AN. Heifers fed H and AH lost weight, but heifers fed AH had 50% (P less than .05) less daily weight loss than those fed H. Daily gain increased (P less than .05) incrementally in response to sequential supplement additions of cottonseed meal (AH vs HP; -.10 vs .17 kg), ground corn (HP vs HPE; .17 vs .29 kg) and monensin (HPE vs HPEM; .29 vs .39 kg). Hay DM intake relative to body weight and DDMI were increased (P less than .01) by ammoniation. Intake did not differ between HPE and HPEM. Diet affected age at puberty (P less than .05), which decreased with increased dietary components. Weight differences among diet groups following the winter feed trial were largely eliminated prior to breeding. Nevertheless, H- and AH-fed heifers collectively weighed less (P less than .01) prior to breeding than did heifers of supplemented diet groups. Reproductive development tended to be adversely affected by weight loss during the postweaning period.