Synaptic and non-synaptic mechanisms underlying low calcium bursts in the in vitro hippocampal slice

Summary 1. The epileptiform activity generated by lowering extracellular [Ca⁺⁺] was studied in the CA1 subfield of rat hippocampal slices maintained in vitro at 32° C. Extracellular and intracellular recordings were performed with NaCl and KCl filled microelectrodes. 2. Synaptic potentials evoked by stimulation of the stratum radiatum and alveus were blocked upon perfusion with artificial cerebrospinal fluid (ACSF) containing 0.2 mM Ca⁺⁺, 4 mM Mg⁺⁺. Blockade of synaptic potentials was accompanied by the appearance of synchronous field bursts which either occurred spontaneously or could be induced by stimulation of the alveus. 3. Both spontaneous and stimulus-induced low Ca⁺⁺ bursts recorded extracellularly in stratum pyramidale consisted of a negative potential shift with superimposed population spikes. This extracellular event was closely associated with intracellularly recorded action potentials rising from a prolonged depolarization shift. Steady hyperpolarization of the cell membrane potential decreased the amplitude of the depolarizing shift suggesting that synaptic conductance were not involved in the genesis of the low Ca⁺⁺ burst. 4. Spontaneous depolarizing inhibitory potentials recorded in normal ACSF with KCl filled microelectrodes were reduced in size in low Ca⁺⁺ ACSF. However, small amplitude potentials could still be observed at a time when low Ca⁺⁺ bursts were generated by hippocampal CA1 pyramidal neurons. 5. Bicuculline methiodide, an antagonist of -aminobutyric acid (GABA), was capable of modifying the frequency of occurrence and the shape of synchronous field bursts. The effects evoked by bicuculline methiodide were, however, not observed when 81–100% of NaCl was replaced with Na-Methylsulphate. Hence, it was concluded that in low Ca⁺⁺ ACSF even though large release of transmitter such as those following electrical activation of stratum radiatum or alveus cannot be observed, small spontaneous release of the inhibitory transmitter GABA seems to persist. 6. Substitution of NaCl with Na-Methylsulphate also caused changes in the synchronous field bursts which were different from those observed following application of bicuculline methiodide. These findings suggest that in low Ca⁺⁺ ACSF, in addition to residual GABAergic Cl^- mechanisms, non-synaptic Cl^- conductances might play a role in controlling the excitability of hippocampal neurons.Supported by grants from the MRC of Canada (MA-8109) and Sick Children Foundation to MA     

Radiotherapy alone in breast cancer. I. Analysis of tumor parameters, tumor dose and local control: the experience of the Gustave-Roussy Institute and the Princess Margaret Hospital

This retrospective study involved 463 breast cancer patients treated by radiotherapy alone at the Princess Margaret Hospital and at the Institut Gustave-Roussy. These patients either had operable tumors, but were unfit for general anesthesia, or had inoperable tumors due to local contraindications to surgery. Results were analyzed according to tumor response, local recurrence rate, tumor size, tumor fixation, nodal fixation and tumor dose. Conventional statistical analysis of local control showed two significant factors: tumor dose and tumor size. Multivariate analysis permitted to define an "individual risk" (IR) of local recurrence according to three independent factors: tumor size, tumor fixation, and nodal fixation. It was shown that the IR was a good prognostic factor for local control. Increase in tumor dose gave a similar effect in the local recurrence relative risk for all the IR groups. According to the slope of the dose-effect curve, it was deduced that a dose increase of 15 Gy can decrease the relative risk of local recurrence 2-fold. In fact, it was shown that tumor dose was the most significant independent factor on local control, able to produce up to a 10-fold increase compared to 2-fold decrease for tumor size. If the IR of local recurrence is known, a theoretical predictive value on local control, taking into account the tumor dose, can be determined according to the present data.     

Caffeine actions on currents induced by calcium-overload in Purkinje fibers

The ionic events underlying the changes induced by caffeine in calcium-overloaded Purkinje fibers were studied by means of a voltage-clamp technique. The following results were obtained. In fibers exposed to strophanthidin (5 X 10(-7) M), a depolarizing clamp of suitable magnitude or duration is followed by an oscillatory current (Ios) often superimposed on a decaying inward tail current (the "tail current"). Caffeine (9 mM) abolishes Ios and increases the tail current. Caffeine has similar actions when calcium overload is induced by increasing [Ca]0 or decreasing [Na]0. The magnitude of the tail current is reduced by decreasing [Ca]0. The tail current appears with repolarizations to -40 mV or more negative values as Ios appears in the absence of caffeine. As with Ios the tail current can be triggered twice (during and after a test clamp of suitable characteristics), becomes more inward with repeated clamps and becomes larger with larger or longer conditioning clamps. During the recovery from caffeine exposure, the tail current decreases gradually as Ios returns progressively. It is concluded that both Ios and tail current are caused by calcium overload but are affected in opposite direction by caffeine, apparently because caffeine decreases the calcium overload in the sarcoplasmic reticulum (abolition of Ios) and increases the calcium to be extruded from the sarcoplasm (increase in the tail current).     

Primary intermediates of rhodopsin studied by low temperature spectrophotometry and laser photolysis. Bathorhodopsin, hypsorhodopsin and photorhodopsin

The primary photochemical processes of rhodopsin studied by low temperature spectrophotometry and picosecond laser spectroscopy in our group was summarized. Low temperature spectroscopic experiments demonstrated that the retinylidene chromophores of hypso- and bathorhodopsins are in a twisted all-trans forms. Excitation of rhodopsin with 532 nm laser pulse (width: 25 psec) yielded a new bathochromic photoproduct "photorhodopsin"; its spectrum was located at longer wavelengths than that of bathorhodopsin. Photorhodopsin decays to bathorhodopsin with time constants of about 200 psec in squid and 40 psec in cattle. Squid and octopus hypsorhodopsins were produced within 25 psec by high energy pulse, but not by low energy pulse. Thus hypsorhodopsin is produced by two photon reactions (sequential two photochemical reactions) and decayed to bathorhodopsin with time constant of 125 psec.     

低分子肝素钙抗凝对多囊卵巢综合征所致不孕症患者来曲唑诱导排卵疗效的影响

目的分析低分子肝素钙抗凝对多囊卵巢综合征(PCOS)所致不孕症患者来曲唑诱导排卵疗效的影响。方法选取2014年1月—2019年1月九江市第三人民医院和彭泽县妇幼保健院收治的156例PCOS所致不孕症患者,采用随机数字表分成两组,每组78例。对照组口服来曲唑治疗,观察组采取口服来曲唑联合低分子肝素钙注射液治疗。比较两组的疗效、子宫内膜容受性、凝血功能指标、促排卵结局及不良反应。结果观察组总有效率[94.87%(74/78)]显著高于对照组[80.77%(63/78)],差异有统计学意义(χ²=7.252,P=0.007)。治疗后,观察组子宫内膜厚度、子宫动脉搏动指数(PI)及阻力指数(RI)分别为(9.75±1.03)mm、(1.30±0.26)及(0.58±0.12),对照组子宫内膜厚度、PI及RI分别为(7.48±0.95)mm、(1.71±0.33)及(0.66±0.11),两组比较差异均有统计学意义(t=14.308,8.619,4.340,均P<0.05)。治疗后,两组凝血功能指标比较差异均有统计学意义(均P<0.05)。观察组妊娠率[52.56%(41/78)]显著高于对照组[32.05%(25/78)],自然流产率[2.44%(1/41)]显著低于对照组[16.00%(4/25)],差异均有统计学意义(均P<0.05)。观察组不良反应发生率[16.67%(13/78)]与对照组[12.82%(10/78)]比较差异无统计学意义(χ²=0.459,P=0.498)。结论PCOS所致不孕症患者在应用来曲唑诱导排卵的同时联合低分子肝素钙抗凝治疗能有效改善患者的凝血-纤溶状态,明显提高患者的子宫内膜容受性,改善促排卵结局。     

Identifying children at risk of intellectual disability in UNICEF’s multiple indicator cluster surveys: Cross-sectional survey

BackgroundResearch on intellectual disability has been criticized for primarily addressing the situation of people in high-income countries.Objective/Hypothesis. To determine whether MICS6 data on ‘functional difficulty associated with learning’ (FDAL) in low- and middle-income countries could be used as a proxy indicator for intellectual disability.MethodsSecondary analysis of nationally representative data collected in Round 6 of UNICEF’s Multiple Indicator Cluster Surveys (MICS) on 244,915 children in 18 middle- and low-income countries.ResultsThe prevalence of FDAL in middle- and low-income countries was broadly similar to the estimated prevalence of intellectual disability in high-income countries. The association between risk of FDAL and household wealth was weak, with alternative measures of developmental delay showing significantly stronger associations with household wealth. The risk of making potential false negative errors in identifying FDAL increases as household wealth and level of maternal education decrease. The risk of making potential false positive errors in identifying FDAL is greater among more highly educated respondents, although this association is only statistically significant among older children.ConclusionsThe use of FDAL as a proxy indicator for intellectual disability cannot be recommended given: (1) it would probably underestimate the overall prevalence of intellectual disability in middle and low income countries; and (2) it is likely to be overestimate prevalence among families with higher socio-economic position (SEP) and underestimate prevalence among families with lower SEP.     

Child developmental and special education service receipt: The intersection of health and poverty

BackgroundChildren born of low birth weight (LBW) and/or premature may have developmental delays and difficulties. The vulnerability, without early intervention, would have detrimental lifelong effects.ObjectivesThis study examined 1) the relationship between LBW and prematurity and the occurrence and timing of children's receipt of developmental and special education services; and 2) whether poverty intersects with LBW and prematurity affecting service receipt.MethodsThis population-based study used cross-sectional data from the National Survey of Children's Health which consisted of approximately 52,000 participants aged 1–17 between 2017 and 2018 in the United States. We conducted logistic regression to analyze the predictive relationship of LBW/prematurity and the occurrence of receiving developmental and special education services. We then conducted ordered logistic regression to examine whether LBW and prematurity predicted the timing of receiving developmental and special education services. Further, we conducted moderating analyses to examine whether the predictive relationships above varied with poverty. The analyses listed above were weighted to reflect the population drawn.ResultsChildren born with LBW and prematurity were more likely to receive developmental and special education services and they tended to receive services earlier than those born at normal weight and term. Educational disparities were evident among children in low-income families. Children of LBW in low-income families were less likely to receive earlier services than those in affluent families.ConclusionsThis study indicates developmental and special education needs of children born LBW and/or premature. With restrained assets, low-income families may need more assistance to promote optimal development for their children.     

The Australian Obesity Management Algorithm: A simple tool to guide the management of obesity in primary care

Obesity is a complex and multifactorial chronic disease with genetic, environmental, physiological and behavioural determinants that requires long-term care. Obesity is associated with a broad range of complications including type 2 diabetes, cardiovascular disease, dyslipidaemia, metabolic associated fatty liver disease, reproductive hormonal abnormalities, sleep apnoea, depression, osteoarthritis and certain cancers. An algorithm has been developed (with PubMed and Medline searched for all relevant articles from 1 Jan 2000–1 Oct 2021) to (i) assist primary care physicians in treatment decisions for non-pregnant adults with obesity, and (ii) provide a practical clinical tool to guide the implementation of existing guidelines (summarised in Appendix 1) for the treatment of obesity in the Australian primary care setting.Main recommendations and changes in managementTreatment pathways should be determined by a person’s anthropometry (body mass index (BMI) and waist circumference (WC)) and the presence and severity of obesity-related complications. A target of 10–15% weight loss is recommended for people with BMI 30–40 kg/m² or abdominal obesity (WC > 88 cm in females, WC > 102 cm in males) without complications. The treatment focus should be supervised lifestyle interventions that may include a reduced or low energy diet, very low energy diet (VLED) or pharmacotherapy. For people with BMI 30–40 kg/m² or abdominal obesity and complications, or those with BMI > 40 kg/m² a weight loss target of 10–15% body weight is recommended, and management should include intensive interventions such as VLED, pharmacotherapy or bariatric surgery, which may be required in combination. A weight loss target of > 15% is recommended for those with BMI > 40 kg/m² and complications and they should be referred to specialist care. Their treatment should include a VLED with or without pharmacotherapy and bariatric surgery.     

快速大量分离血浆低密度脂蛋白亚组分的方法

目的 :研究快速大量分离低密度脂蛋白亚组分的方法。方法 :通过2步超速离心法分离LDL亚组分 ,并用电泳法及电镜观察鉴定2种亚组分。结果 :仅用10h就将LDL亚组分分开 ,并证实经分离的2种亚组分为纯品。结论 :本方法是1种分离LDL亚组分较好方法     

介入联合手术治疗膀胱癌32例疗效分析

目的观察髂内动脉灌注化疗联合手术治疗膀胱癌的疗效。方法对32例中晚期膀胱癌先行介入治疗,再手术切除。结果32例膀胱癌完全缓解(CR)率为71．9％。结论介入治疗中晚期膀胱的手术提供了良好基础,对一部分原本行扩大切除术甚至全切的患实行单纯部分切除术,从而保留了膀胱生理功能,有助于提高患生活质量,延长生命。